Análisis bibliométrico de la investigación en genética y la ruptura de ligamento cruzado anterior en deporte: una revisión / Bibliometric analysis of research in genetic and anterior cruciate ligament rupture in sport: a review / Análise bibliométrica da pesquisa em genética e ruptura do ligamento cruzado anterior no esporte: uma revisão

Resumen: Introducción: El componente genético se ha establecido como un factor de riesgo considerable para la ruptura del ligamento cruzado anterior (RLCA). La investigación actual se ha centrado en conocer los genes candidatos que pueden influir y predisponer a un sujeto a padecer esta lesión. Objetivo: Se llevó a cabo un análisis bibliométrico para rastrear los resultados de la indagación e identificar las tendencias globales, así como las brechas en el conocimiento sobre la relación entre el componente genético y la RLCA. Metodología: Los datos fueron extraídos de las bases Pubmed y Scopus, igual que analizados en el paquete Bibliometrix del software R. Se identificó un total de 63 estudios publicados a partir del 2007. Resultados: La mayoría de las publicaciones identificadas fueron artículos de investigación (85.71 %). Los autores con mayor número de aquellas se encuentran en Polonia y Sudáfrica. El análisis a través del mapa de coocurrencias reveló que hay una línea principal de investigación basada en el estudio de polimorfismos genéticos, especialmente en los genes de las familias del colágeno (COL1A1, COL5A1, COL12A1, en mayor frecuencia). Un total de 54 genes candidatos fueron identificados en los estudios. Conclusión: Esperamos que este estudio pueda contribuir a encontrar puntos claves y vacíos de investigación, al proporcionar análisis integrales e información estructurada sobre este tema.

Abstract: Introduction: Genetic component has been established as a significant risk factor for anterior cruciate ligament rupture (ACLR). Current research has focused on knowing the candidate genes that can influence and predispose a subject to this injury. Objective: A bibliometric analysis was carried out to trace the results of the research and identify global trends and gaps in knowledge about the relationship between the genetic component and ACLR. Methodology: Data were extracted from the Pubmed and Scopus databases and analyzed in the Bibliometrix package of the R software. A total of 63 studies published since 2007 were identified. Results: Most of the publications recovered were research articles (85.71%). The authors with the highest number of those are in Poland and South Africa. The analysis through the co-occurrence map reveals that there is a mainline of research based on the study of genetic polymorphisms, especially in the genes of the collagen families (COL1A1, COL5A1, COL12A1, in greater frequency). A total of 54 candidate genes were identified within the studies. Conclusion: We hope that this study can help to find key points and research gaps by providing a comprehensive analysis and structured information on this topic.

Resumo: Introdução: O componente genético foi estabelecido como um fator de risco significativo para a ruptura do ligamento cruzado anterior (RLCA). As pesquisas atuais têm se concentrado em identificar os genes candidatos que podem influenciar e predispor um indivíduo a essa lesão. Objetivo: Foi realizada uma análise bibliométrica para rastrear os resultados das pesquisas e identificar tendências globais e lacunas no conhecimento sobre a relação entre o componente genético e a RLCA. Metodologia: Os dados foram extraídos das bases de dados Pubmed e Scopus e analisados no pacote Bibliometrix do software R. Um total de 63 estudos publicados desde 2007 foram identificados. Resultados: A maioria das publicações recuperadas foram artigos de pesquisa (85,71%). Os autores com o maior número dessas publicações estão na Polônia e na África do Sul. A análise por meio do mapa de coocorrência revela que há uma linha principal de pesquisa baseada no estudo de polimorfismos genéticos, especialmente nos genes das famílias de colágeno (COL1A1, COL5A1, COL12A1, com maior frequência). Um total de 54 genes candidatos foram identificados nos estudos. Conclusão: Esperamos que este estudo possa ajudar a encontrar pontos-chave e lacunas de pesquisa, fornecendo uma análise abrangente e informações estruturadas sobre este tema.

Differences in Muscle Strength Performance According to the Genotypes of the rs4646994 Polymorphism of the ACE Gene in a Sedentary Population / Diferencias en el Rendimiento de la Fuerza Muscular Según los Genotipos del Polimorfismo rs4646994 del Gen ACE en una Población Sedentaria

SUMMARY: The angiotensin converting enzyme gene (ACE) has been associated with endurance and strength performance through its I/D polymorphism. Nevertheless, contradictory results exist between different populations. In this context, the purpose of this research was to determine the influence of the I/D polymorphism of the ACE gene on muscle strength in a sedentary Chilean sample. In this study 102 healthy male students (21.3 ± 2.2 years) completed the assessment. I/D genotyping, cardiovascular, anthropometric, grip strength and knee extensor peak strength were evaluated. The ACE polymorphism frequency was: II, 33.3 %; ID, 46.1 %; DD, 20.6 %. The results showed significant differences and large effect size in maximum (p = 0.004; d = 0.85) and relative handgrip strength (p = 0.004; d = 0.9) between genotype II vs DD. No difference was found for maximal or relative knee extensor strength between groups (p = 0.74), showing a low effect size (d = 0.20). In conclusion, this study provides insights into the role of the ACE gene in muscle strength and highlights the importance of investigating genetic variants in sedentary populations to better understand strength performance.

El gen de la enzima convertidora de angiotensina (ACE) se ha asociado con el rendimiento de resistencia y fuerza a través de su polimorfismo I/D. Sin embargo, existen resultados contradictorios entre diferentes poblaciones. En este contexto, el propósito de esta investigación fue determinar la influencia del polimorfismo I/D del gen ACE sobre la fuerza muscular en una muestra chilena sedentaria. En este estudio, fueron evaluados 102 estudiantes varones sanos (21,3 ± 2,2 años). Se realizaron aplicaron las siguientes evaluaciones: genotipado del polimorfismo I/D, cardiovascular, antropométrica, fuerza de prensión y fuerza máxima de extensión de rodilla. La frecuencia del polimorfismo I/D de ACE fue: II, 33,3 %; DNI, 46,1 %; DD, 20,6 %. Los resultados mostraron diferencias significativas y un gran tamaño del efecto en la fuerza máxima (p = 0,004; d = 0,85) y relativa de prensión manual (p = 0,004; d = 0,9) entre el genotipo II y el DD. No se encontraron diferencias en la fuerza máxima o relativa de los extensores de rodilla entre los grupos (p = 0,74), lo que muestra un tamaño de efecto bajo (d = 0,20). En conclusión, este estudio proporciona información sobre el papel del gen ACE en la fuerza muscular y destaca la importancia de investigar variantes genéticas en poblaciones sedentarias para comprender mejor el rendimiento de la fuerza.

Sprint and Anaerobic Power with the Soccer-Specific ACTN3 Gene: A Distintive Example / Sprint y Potencia Anaeróbica con el Gen ACTN3 Específico del Fútbol: Un Ejemplo Distintivo

SUMMARY: The aim of this study is twofold: (1) to identify differences in certain anaerobic parameters (10m sprint, 30m sprint, anaerobic power, and Illinois agility tests) between professional and amateur soccer players, and (2) to determine whether there is a difference in the ACTN3 gene polymorphism between professional and amateur soccer players. Ultimately, the goal is to reveal which parameters contribute to the differentiation in these two aspects. A total of 133 volunteer soccer players, including 71 professionals and 62 amateurs, participated in the research. DNA extraction from buccal epithelial cells was performed using a commercial kit to determine the genetic background of the athletes, and Real-Time PCR was conducted for genotyping. Statistical analysis of the findings obtained from the test results was performed using the SPSS 23 (SPSS Inc., Chicago, IL, USA) package program. The homogeneity of variance of the data was assessed using the Levene Test, and normal distribution analyses were conducted using the Shapiro-Wilk Test. Chi-square and Mann-Whitney U tests were employed for parameter analysis. The significance level was set at p0.05). However, there is a statistically significant difference in anaerobic parameters (10m sprint, 30m sprint, and anaerobic power) except for the Illinois test (p<0.05). In conclusion, our study found that gene polymorphism is not a differentiating factor between professional and amateur soccer players, but speed (10m and 30m) and anaerobic power parameters are differentiating factors.

Los objetivos de este estudio fueron: 1º identificar diferencias en ciertos parámetros anaeróbicos (sprint de 10 m, sprint de 30 m, potencia anaeróbica y pruebas de agilidad de Illinois) entre jugadores de fútbol profesionales y amateurs, y 2º determinar si existe una diferencia en el polimorfismo del gen ACTN3 entre jugadores de fútbol profesionales y aficionados. En definitiva, el objetivo fue revelar qué parámetros contribuyen a la diferenciación en estos dos aspectos. En la investigación participaron un total de 133 jugadores de fútbol voluntarios, incluidos 71 profesionales y 62 aficionados. La extracción de ADN de las células epiteliales orales se realizó utilizando un kit comercial para determinar los antecedentes genéticos de los atletas y se realizó una PCR en tiempo real para el genotipado. El análisis estadístico de los hallazgos obtenidos a partir de los resultados de las pruebas se realizó utilizando el programa de paquete SPSS 23 (SPSS Inc., Chicago, IL, EE. UU.). La homogeneidad de la varianza de los datos se evaluó mediante la prueba de Levene y los análisis de distribución normal se realizaron mediante la prueba de Shapiro-Wilk. Para el análisis de parámetros se emplearon las pruebas de Chi-cuadrado y U de Mann-Whitney. El nivel de significancia se fijó en p0,05). Sin embargo, existe una diferencia estadísticamente significativa en los parámetros anaeróbicos (sprint de 10 m, sprint de 30 m y potencia anaeróbica) excepto para la prueba de Illinois (p<0,05). En conclusión, nuestro estudio encontró que el polimorfismo genético no es un fac- tor diferenciador entre jugadores de fútbol profesionales y amateurs, pero sí los parámetros de velocidad (10 m y 30 m) y potencia anaeróbica.

Association of IGF-1 and IGF-2 genotypes with respiratory muscle strength in individuals with COPD: a cross-sectional study / Asociación de los genotipos de IGF-1 e IGF-2 con la fuerza muscular respiratoria en individuos con EPOC: estudio transversal

INTRODUCTION: Chronic obstructive pulmonary disease is a systemic disease characterized not only by respiratory symptoms but also by physical deconditioning and muscle weakness. One prominent manifestation of this disease is the decline in respiratory muscle strength. Previous studies have linked the genotypes of insulin-like growth factor 1 and 2 (IGF-1 and IGF-2) to muscle weakness in other populations without this disease. However, there is a notable knowledge gap regarding the biological mechanisms underlying respiratory muscle weakness, particularly the role of IGF-1 and IGF-2 genotypes in this pulmonary disease. Therefore, this study aimed to investigate, for the first time, the association between IGF-1 and IGF-2 genotypes with respiratory muscle strength in individuals with chronic obstructive pulmonary disease. In addition, we analyzed the relationship between oxidative stress, chronic inflammation, and vitamin D with respiratory muscle strength. METHODS: A cross sectional study with 61 individuals with chronic obstructive pulmonary disease. Polymerase chain reaction of gene polymorphisms IGF-1 (rs35767) and IGF-2 (rs3213221) was analyzed. Other variables, related to oxidative stress, inflammation and Vitamin D were dosed from peripheral blood. Maximal inspiratory and expiratory pressure were measured. RESULTS: The genetic polymorphisms were associated with respiratory muscle strength ( 3.0 and 3.5; = 0.57). Specific genotypes of IGF-1 and IGF-2 presented lower maximal inspiratory and expiratory pressure (<0.05 for all). Oxidative stress, inflammatory biomarkers, and vitamin D were not associated with respiratory muscle strength. CONCLUSION: The polymorphisms of IGF-1 and IGF-2 displayed stronger correlations with respiratory muscle strength compared to blood biomarkers in patients with chronic obstructive pulmonary disease. Specific genotypes of IGF-1 and IGF-2 were associated with reduced respiratory muscle strength in this population.

INTRODUCCIÓN: La enfermedad pulmonar obstructiva crónica es una enfermedad sistémica caracterizada no solo por síntomas respiratorios, sino también por el deterioro físico y la debilidad muscular. Una manifestación destacada de esta enfermedad es el declive en la fuerza de los músculos respiratorios. Estudios previos han vinculado los genotipos de factor de crecimiento insulínico 1 y 2 (IGF-1 e IGF-2) con la debilidad muscular en poblaciones sin esta enfermedad. Sin embargo, existe un vacío de conocimiento con respecto a los mecanismos biológicos subyacentes a la debilidad de los músculos respiratorios, en particular el papel de los genotipos IGF-1 e IGF-2 en esta enfermedad pulmonar. Por lo tanto, este estudio tuvo como objetivo investigar, por primera vez, la asociación de los genotipos IGF-1 e IGF-2 con la fuerza de los músculos respiratorios en individuos con enfermedad pulmonar obstructiva crónica. Además, analizamos la relación entre el estrés oxidativo, la inflamación crónica y la vitamina D con la fuerza de los músculos respiratorios. MÉTODOS: Un estudio transversal con 61 individuos con enfermedad pulmonar obstructiva crónica. Se analizó la reacción en cadena de la polimerasa de los polimorfismos genéticos IGF-1 (rs35767) e IGF-2 (rs3213221). Otras variables relacionadas con el estrés oxidativo, la inflamación y la vitamina D se dosificaron a partir de muestras de sangre periférica. Se midieron las presiones inspiratorias y espiratorias máximas. RESULTADOS: Los polimorfismos genéticos están asociados con la fuerza de los músculos respiratorios (F: 3.0 y 3.5; R2= 0.57). Genotipos específicos de IGF-1 e IGF-2 presentaron bajos valores en las presiones inspiratorias y espiratorias (p<0.05 en todos los casos). El estrés oxidativo, los biomarcadores inflamatorios y la vitamina D no se asociaron con la fuerza de los músculos respiratorios. CONCLUSIÓN: Los polimorfismos de IGF-1 e IGF-2 mostraron correlaciones más sólidas con la fuerza de los músculos respiratorios en pacientes con enfermedad pulmonar obstructiva crónica en comparación con los biomarcadores sanguíneos. Genotipos específicos de IGF-1 e IGF-2 se asociaron con una disminución de la fuerza de los músculos respiratorios en esta población.

Frequência e distribuição do gene da α-actinina-3 e sua associação em atletas brasileiras de voleibol / Frequency and distribution of the α -actinin-3 gene and its association in brazilian volleyball athletes

Introduction: The ACTN3 gene encodes the α-actinin-3 protein in the Z lines of the sarcomere, which anchors the actin protein in the contractile apparatus, present exclusively in type II muscle fibers, presenting greater glycolytic capacity, which is essential for sports with high-energy actions. intensity and short duration as is the case with Volleyball. Objective: To verify the frequency and distribution of the ACTN3 gene, RR and RX genotypes that express α-actinin-3 (EX α-actinin-3), and XX genotype that do not express α-actinin-3 (NE α-actinin-3) and its association with Brazilian volleyball athletes. Materials and Methods: Nine-seven (97) athletes from the women's volleyball super league took part in the study. Body mass, height and age were evaluated to characterize the sample. Salivary samples were analyzed using (PCR) in real time, to determine the genotypes, and, to verify the association of the genotype with the status of volleyball athlete in the three categories (National Teams, Brazilian National Team and Brazilian Olympic Team), the test was carried out Chi-square of independence (χ²). To obtain the odds ratio of the outcome, a log linear regression analysis was performed. All tests were carried out using the JAMOVI 2.4 (2023) statistical software. Results: Among the athletes in the sample competing in the National Teams competition, 91.8% have the EX-α-actinin-3 genotype. When we consider Brazilian National Team competitions, 93.7% have the EX-α-actinin-3 genotype. Athletes who play for the Brazilian Olimpic Team, 100% of the sample have the EX-α-actinin-3 genotype. Considering that in the world population, the frequency is 80%, it is possible to verify that as you approach the athletes who participate in the women's team there is a greater participation of athletes with the EX-α-actinin-3 genotype. Furthermore, there was an association between the genotypes that EX α-actinin-3 and the National category, with the status of elite athlete, where (χ²) obtained the p value (0.023) and the rate ratio (2.71) for the outcome of the genotypes (EX α-actinin-3) being elite athletes. Conclusion: The athlete's genetic characteristics, environment, nutrition, physical, technical and tactical preparation are some of the factors that contribute to sports performance. However, the results of the present study suggest that athletes with RR and RX genotypes that express α-actinin-3, present in type II muscle fibers, seem to confer an advantage when playing high-performance volleyball.

Polimorfismo Ser326Cis de la 8-oxoguanina ADN glucosilasa 1 (OGG1) en hombres con teratozoospermia / Ser326Cys polymorphism of 8-oxoguanine DNA glycosylase 1 (OGG1) in men with teratozoospermia

Resumen Antecedentes: El incremento seminal de especies reactivas de oxígeno (ERO) se ha vinculado con la oxidación del ADN y anormalidades en la morfología espermática. La enzima 8-oxoguanina ADN glucosilasa 1 (OGG1) repara la oxidación del ADN. Sin embargo, la presencia del polimorfismo en la OGG1 que involucra cambio de citocina (C) por guanina (G), resultando la sustitución de una cisteína por una serina en el codón 326 (Ser326Cis), ha demostrado disminución en la reparación del ADN oxidado. Estudios del polimorfismo Ser326Cis en hombres españoles y asiáticos con infertilidad demostraron que el alelo G(Cis) incrementa las ERO, impactando en la infertilidad y en la teratozoospermia. Objetivo: Conocer la prevalencia del polimorfismo Ser326Cis de OGG1 en pacientes con teratozoospermia. Método: Se analizaron parámetros espermáticos y el polimorfismo Ser326Cis de OGG1 de 81 muestras de semen con teratozoospermia. Resultados: Los genotipos detectados fueron Ser326Ser(CC) 43%, Ser326Cis(CG) 41% y Cis326Cis(GG) 16%. La frecuencia del alelo G(Cis) fue de 0.4, valor mayor a la frecuencia reportada en las bases de datos disponibles para poblaciones americanas (0.21-0.29), los parámetros espermáticos no se relacionaron con el polimorfismo Ser326Cis. Conclusión: El alelo G(Cis) es un factor que contribuye a la infertilidad.

Abstract Background: The increase in seminal reactive oxygen species (ROS) has been linked to DNA oxidation and abnormalities in sperm morphology. The enzyme 8-oxoguanine DNA glycosylase 1 (OGG1) repairs DNA oxidation. However, the presence of the polymorphism in OGG1 that involves a change of cytokine (C) to guanine (G) resulting in the substitution of a cystine for serine at codon 326 (Ser326Cys) has shown a decrease in the repair of oxidized DNA. Studies of the Ser326Cys polymorphism in Spanish and Asian men with infertility demonstrated that the G(Cys) allele increases ROS, impacting infertility and teratozoospermia. Objective: To know the prevalence of the Ser326Cys polymorphism of OGG1 in patients with teratozoospermia. Method: Sperm parameters and the Ser326Cys polymorphism of OGG1 were analyzed from 81 semen samples. Results: The genotypes detected were Ser326Ser(CC) 43%, Ser326Cys(CG) 41%, and yis326Cys(GG) 16%. The frequency of the G allele (Cys) was 0.4, a value higher than the frequency reported in the databases available for American populations (0.21-0.29), the sperm parameters were not related to the Ser326Cys polymorphism. Conclusion: The G (Cys) allele is a factor that contributes to infertility.

Descripción de polimorfismos genéticos en CYP3A5 y MDR-1 y su impacto en el rechazo agudo clínico de pacientes trasplantados de hígado del Hospital San Vicente Fundación Rionegro / Description of genetic polymorphisms in CYP3A5 and MDR-1 and their impact on clinical acute rejection in liver transplant patients at Hospital San Vicente Fundación Rionegro

Introducción. El tacrolimus es un medicamento inmunosupresor ampliamente usado en trasplante hepático, que presenta una gran variabilidad interindividual la cual se considera asociada a la frecuencia de polimorfismos de CYP3A5 y MDR-1. El objetivo de este estudio fue evaluar la frecuencia de los polimorfismos rs776746, rs2032582 y rs1045642 y su asociación con rechazo clínico y toxicidad farmacológica. Métodos. Se incluyeron pacientes inmunosuprimidos con tacrolimus a quienes se les realizó trasplante hepático en el Hospital San Vicente Fundación Rionegro entre 2020 y 2022, con supervivencia mayor a un mes. Se evaluaron las variables clínicas, rechazo agudo y toxicidad farmacológica. Se secuenciaron los genes de estudio mediante PCR, comparando la expresión o no en cada uno de los pacientes. Resultados. Se identificaron 17 pacientes. El 43 % de los pacientes se clasificaron como CYP3A5*1/*1 y CYP3A5*1/*3, entre los cuales se encontró asociación con aumento en la tasa de rechazo agudo clínico, al comparar con los pacientes no expresivos (100 % vs. 44 %, p=0,05); no hubo diferencias en cuanto a la toxicidad farmacológica u otros desenlaces. Se encontró el polimorfismo rs2032582 en un 50 % y el rs1045642 en un 23,5 % de los pacientes, sin embargo, no se identificó asociación con rechazo u otros eventos clínicos. Conclusiones. Se encontró una asociación entre el genotipo CYP3A5*1/*1 y CYP3A5*1/*3 y la tasa de rechazo clínico. Sin embargo, se requiere una muestra más amplia para validar estos datos y plantear modelos de medicina personalizada.

Introduction. Tacrolimus is an immunosuppressive drug widely used in liver transplantation, which presents great interindividual variability which is considered associated with the frequency of CYP3A5 and MDR-1 polymorphisms. The objective of this study was to evaluate the frequency of the rs776746, rs2032582 and rs1045642 polymorphisms and their association with clinical rejection and drug toxicity. Methods. Immunosuppressed patients with tacrolimus who underwent a liver transplant at the Hospital San Vicente Fundación Rionegro between 2020 and 2022 were included, with survival of more than one month. Clinical variables, acute rejection and pharmacological toxicity were evaluated. The study genes were sequenced by PCR, comparing their expression or not in each of the patients. Results. Seventeen patients were identified. 43% of the patients were classified as CYP3A5*1/*1 and CYP3A5*1/*3, among which an association was found with increased rates of clinical acute rejection when compared with non-expressive patients (100% vs. 44%, p=0.05). There were no differences in drug toxicity or other outcomes. The rs2032582 polymorphism was found in 50% and rs1045642 in 23.5% of patients; however, no association with rejection or other clinical events was identified. Conclusions. An association was found between the CYP3A5*1/*1 and CYP3A5*1/*3 genotype and the clinical rejection rate. However, a larger sample is required to validate these data and propose models of personalized medicine.

ABCG2 polymorphism and rivaroxaban pharmacokinetics in healthy individuals after a single dose

Rivaroxaban is a direct factor Xa inhibitor. Its interindividual variability is large and may be connected to the occurrence of adverse drug reactions or drug inefficacy. Pharmacogenetics studies concentrating on the reasons underlying rivaroxaban's inadequate response could help explain the differences in treatment results and medication safety profiles. Against this background, this study evaluated whether polymorphisms in the gene encoding the ABCG2 transporter modify the pharmacokinetic characteristics of rivaroxaban. A total of 117 healthy volunteers participated in two bioequivalence experiments with a single oral dose of 20 mg rivaroxaban, with one group fasting and the other being fed. Ultra-high-performance liquid chromatography coupled with mass spectrometry was employed to determine the plasma concentrations of rivaroxaban, and the WinNonlin program was used to calculate the pharmacokinetics parameters. In the fasting group, the rivaroxaban pharmacokinetic parameters of Vd (508.27 vs 334.45 vs 275.59 L) and t1/2 (41.04 vs 16.43 vs 15.47 h) were significantly higher in ABCG2 421 A/A genotype carriers than in ABCG2 421 C/C and 421 C/A genotype carriers (P<0.05). The mean values of Cmax (145.81 vs 176.27 vs 190.19 ng/mL), AUC0-t (1193.81 vs 1374.69 vs 1570.77 ng/mL·h), and Cl (11.82 vs 14.50 vs 13.01 mL/h) for these groups were lower, but this difference was not statistically significant (P>0.05). These findings suggested that the ABCG2 421 A/A genotype may impact rivaroxaban parameters after a single dose in healthy subjects. This finding must be validated before it is applied in clinical practice.

ACE gene polymorphisms (rs4340) II and DI are more responsive to the ergogenic effect of caffeine than DD on aerobic power, heart rate, and perceived exertion in a homogeneous Brazilian group of adolescent athletes

The purpose of this study was to verify the association between angiotensin-converting enzyme (ACE) genotypes DD, DI, and II and caffeine (CAF) ingestion on endurance performance, heart rate, ratio of perceived exertion (RPE), and habitual caffeine intake (HCI) of adolescent athletes. Seventy-four male adolescent athletes (age: DD=16±1.7; DI=16±2.0; II=15±1.7 years) ingested CAF (6 mg/kg) or placebo (PLA) one hour before performing the Yo-Yo Intermittent Recovery level 1 (Yo-Yo IR1) test. No difference was found among groups for HCI. However, CAF increased the maximal distance covered and VO2max in DI and II genotype carriers compared to PLA (DD: Δ=31 m and 0.3 mL·kg-1·min-1; DI: Δ=286 m and 1.1 mL·kg-1·min-1; II: Δ=160 m and 1.4 mL·kg-1·min-1). Heart rate of DI and II genotype carriers increased with CAF compared to PLA, while RPE was higher in the II and lower in the DD genotypes. The correlations between HCI and maximal distance covered or VO2max were significant in the II genotype carriers with CAF. CAF increased endurance capacity, heart rate, and RPE in adolescent athletes with allele I, while endurance performance and aerobic power had a positive correlation to HCI in the II genotype group. These findings suggested that DD genotype were less responsive to CAF and that genetic variations should be taken into account when using CAF supplementation to enhance exercise performance.

Failure in syndromic management due to drug-resistant Mycoplasma genitalium in Florianópolis, South Brazil / Falha no manejo sindrômico devido a Mycoplasma genitalium resistente em Florianópolis, Sul do Brasil

Introduction: Mycoplasma genitalium is a bacterium associated with sexually transmitted infections that can cause urethritis in men and complications in women, including preterm birth. Increasing macrolide resistance in M. genitalium poses challenges to treatment efficacy. Objective: To present a case of treatment failure of urethritis caused by macrolide-resistant M. genitalium. Case report: This case report describes a 20-year-old man with persistent urethral symptoms despite azithromycin treatment, wherein M. genitalium harbored the A2058G mutation in the 23S rRNA. Subsequent treatment with moxifloxacin resolved symptoms and cleared M. genitalium. Conclusion: The study highlights the importance of resistance testing to guide antimicrobial therapy and emphasizes the need for updated treatment guidelines in Brazil. (AU)

Introdução:Mycoplasma genitalium é uma bactéria associada a infecções sexualmente transmissíveis, que pode causar uretrite em homens e complicações em mulheres, incluindo nascimento prematuro. O aumento da resistência aos macrolídeos em M. genitalium coloca desafios à eficácia do tratamento. Objetivo: Apresentar um caso de falha terapêutica de uretrite causada por M. genitalium resistente aos macrolídeos. Relato de caso: Este relato de caso descreve um homem de 20 anos com sintomas uretrais persistentes, apesar do tratamento com azitromicina, em que M. genitalium possuía a mutação A2058G no rRNA 23S. O tratamento subsequente com moxifloxacino resolveu os sintomas e eliminou M. genitalium. Conclusão: O estudo destacou a importância dos testes de resistência para orientar a terapia antimicrobiana e enfatizou a necessidade de atualizar as diretrizes de tratamento no Brasil. (AU)

Bioinformatic identification of Single Nucleotide Polymorphisms (SNPs) in keratin-associated protein genes in alpacas (Vicugna pacos) / Identificación bioinformática de Polimorfismos de Nucleótido Simple (PNSs) en genes de proteínas asociadas a queratinas en alpacas (Vicugna pacos)

Abstract This study aims to identify single nucleotide polymorphisms (SNPs) within KRTAP genes in alpacas (Vicugna pacos), which play a fundamental role in defining their physico-mechanical properties and potentially the quality of alpaca fiber, the primary product of their breeding. Thirty-four KRTAP genes, as annotated in the reference genome VicPac3.1, were investigated. Utilizing the reference genome, along with nine additional genomes and reads from 300 reduced representation DNA libraries of alpacas, SNPs were identified. Minor allele frequency (MAF) and genotyping rates were computed using PLINK software, while Illumina Scores were determined for each SNP using Illumina Design Studio software. Markers meeting the criteria of MAF ≥ 0.05, genotyping rate > 45%, and Illumina Score ≥ 0.6 per SNP were selected. A total of 67 SNPs were identified within intronic, exonic, and untranslated regions of KRTAP genes. Among these, 35 SNPs were incorporated into the 76K Alpaca SNP microarray, with 32 SNPs subsequently validated in a population of 936 alpacas. In conclusion, our findings delineate SNPs within KRTAPs that hold potential utility in genome-wide association studies, thereby facilitating the integration of modern breeding technologies into alpaca breeding programs.

Resumen Este estudio tiene como objetivo identificar polimorfismos de nucleótido simple (PNSs) dentro de los genes KRTAP en alpacas (Vicugna pacos), que juegan un papel fundamental en la definición de sus propiedades físico-mecánicas y la calidad de la fibra de alpaca, producto principal de su crianza. Se investigaron treinta y cuatro genes KRTAP, tal como están anotados en el genoma de referencia VicPac3.1. Utilizando el genoma de referencia, junto con nueve genomas adicionales y lecturas de 300 bibliotecas de representación reducida de ADN de alpacas, se identificaron los PNSs. La frecuencia de los alelos menores (MAF) y las tasas de genotipificación se calcularon utilizando el software PLINK, mientras que los Illumina Score se determinaron para cada PNS utilizando el software Illumina Design Studio. Se seleccionaron marcadores que cumplían con los criterios de MAF ≥ 0.05, tasa de genotipado > 45% e Illumina Score ≥ 0.6 por PNS. Se identificaron un total de 67 PNSs dentro de regiones intrónicas, exónicas y/o no traducidas de genes KRTAP. Entre estos, se incorporaron 35 PNSs al microarray 76K Alpaca SNP, y posteriormente se validaron 32 PNSs en una población de 936 alpacas. En conclusión, nuestros hallazgos identificaron los PNSs dentro de los KRTAP que tienen una utilidad potencial en estudios de asociación de todo el genoma, facilitando así la integración de tecnologías de reproducción modernas en los programas de reproducción de alpacas.

Relationship between IL-1Ra gene polymorphism and the natural outcome of asymptomatic bacterial vaginosis / 安徽医科大学学报

Objective To investigate the relationship between interleukin 1 receptor a(IL-1Ra)gene polymorphism and different outcomes in asymptomatic bacterial vaginosis(aBV)patients with the aim of grouping and managing aBV patients.Methods In study on the natural attribution of aBV patients,all patients were enrolled and a sam-ple of venous blood and vaginal lavage fluid were separately frozen.After 4 months at the end of the clinical study,patients who completed the study were divided into three groups based on clinical outcomes:self-healing,progres-sive,and unchanged.The IL-1Ra gene polymorphism,the concentration of IL-1 β and IL-1Ra were tested,and the differences in the above indicators among three groups of patients with different outcomes were compared.Results 1 014 Chinese Han female patients were enrolled,and 984 patients completed clinical follow-up and obtained clini-cal outcome data.13 specimens were unusable during testing,with a total of 971 specimens completed the test.IL-1Ra gene was detected in all patients,with three genotypes:A1/A1,A1/A2,and A2/A2.Most population had a genotype of A1/A1,with the rarest genotype being A2/A2.No rare genotype of female was found.The frequency of A2 alleles in the progression group was significantly higher than that in the self-healing group(P＜0.05).IL-1 βand IL-1Ra were detected in all vaginal lavage fluid samples.Compared with the progression group,IL-1 β in the self-healing group was significantly lower(P＜0.05).When carrying the A2 allele,IL-1 β in progression group was relatively low,while the level of IL-1Ra was relatively high.The values of the unchanged group were middle.Con-clusion The polymorphism characteristics of the IL-1Ra gene in aBV patients are related to the IL-1Ra content in vaginal secretions.Carrying allele A2 is related to the elevation of IL-1Ra,the decrease of IL-1 β in vaginal secre-tions.Carrying allele A2 may affect the clinical outcome of aBV by some potential mechanism.

Differential effects of APOE polymorphism in neurotoxicity-responsive astrocytes induced by inflammatory factor / 吉林大学学报(医学版)

Objective:To discuss the differential effects of apolipoprotein E(APOE)gene polymorphism in the neurotoxicity-reactive astrocytes,and to provide the theoretical basis for the study of the pathogenesis of Alzheimer's disease(AD).Methods:The primary cortical astrocytes from the APOE-knockout mice(APOE-/-)were isolated and cultured in vitro,and the purity of the cells was identified by immunofluorescence staining.The human APOE3 and APOE4 recombinant over-expression plasmids were constructed and separately transfected into the primary APOE-/-astrocytes,and the APOE-/-primary cells were regarded as control.Western blotting method was used to detect the expression levels of APOE and glial fibrillary acidic protein(GFAP)proteins in the cells;enzyme-linked immunosorbent assay(ELISA)method was used to detect the APOE level in the cellular culture supernatant.The inflammatory models were prepared with the primary astrocytes transfected with APOE3 and APOE4 and co-stimulated with interleukin-1α(IL-1α),tumor necrosis factor(TNF),and complement C1q.The cells were divided into APOE3+PBS group,APOE4+PBS group,APOE3+IL-1α+TNF+ C1q group,and APOE4+IL-1α+TNF+C1q group.Cell immunofluorescence staining method was used to observe the morphology of the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of glypican 4(Gpc4),glypican 6(Gpc6),thrombospondin 1(Thbs1),thrombospondin 2(Thbs2),SPARC-like protein 1(Sparcl1)and glial cell line derived neurotrophic factor(GDNF),C3,and S100 calcium binding protein B(S100B)mRNA in the cells in various groups;microsphere phagocytosis assay was used to detect the phagocytic capacities of the cells in various groups;Western blotting was used to detect the protein expression levels of B-cell lymphoma 2(Bcl-2),and cysteinyl aspartate specific protease-3(Caspase-3)proteins in the cells in various groups.Results:Compared with APOE-/-group,the expression levels of APOE and GFAP proteins in the cells and the APOE level in the cellular culture supernatant in transfected APOE3 and transfected APOE4 groups were increased(P<0.01).The fluorescence microscope observation results showed that compared with APOE3+PBS and APOE4+PBS groups,the astrocytic processes in APOE3+IL-1α +TNF+Cq1 group and APOE4+IL-1α+TNF+Cq1 group became shorter and the cell bodies became larger;compared with APOE3+IL-1α +TNF+Cq1 group,the astrocytic processes in APOE4+IL-1α +TNF+Cq1 group were even shorter.Compared with APOE3+PBS and APOE4+PBS groups,the expression levels of Gpc4,Gpc6,Thbs1,Thbs2,and Sparcl1 mRNA in the cells in APOE3+IL-1α +TNF+Cq1 group and APOE4+IL-1α +TNF+Cq1 group were significantly decreased(P<0.01);compared with APOE3+IL-1α +TNF+Cq1 group,the expression levels of Gpc4,Gpc6,Thbs1,Thbs2,and Sparcl1 mRNA in the cells in APOE4+IL-1α +TNF+Cq1 group were significantly decreased(P<0.05 or P<0.01).Compared with APOE3+PBS and APOE4+PBS groups,the expression levels of GDNF mRNA in the cells in APOE3+IL-1α+TNF+Cq1 group and APOE4+ IL-1α +TNF+Cq1 group were decreased(P<0.01),and the expression levels of C3 and S100B mRNA were increased(P<0.01);compared with APOE3+IL-1α +TNF+Cq1 group,the expression level of GDNF mRNA in the cells in APOE4+IL-1α+TNF+Cq1 group was decreased(P<0.05),and the expression levels of C3 and S100B mRNA were increased(P<0.05).Compared with APOE3+ PBS group and APOE4+PBS group,the numbers of hagocytosis of microspheres in the cells in APOE3+ IL-1α +TNF+Cq1 group and APOE4+IL-1α +TNF+Cq1 group were significantly decreased;compared with APOE3+IL-1α+TNF+Cq1 group,the number of hagocytosis of microspheres in the cells in APOE4+IL-1α+TNF+Cq1 group was significantly decreased.Compared with APOE3+PBS group and APOE4+PBS group,the expression levels of Bcl-2 protein in the cells in APOE3+IL-1α+TNF+ Cq1 group and APOE4+IL-1α +TNF+Cq1 group were decreased(P<0.05 or P<0.01)and the expression levels of Caspase-3 protein were significantly increased(P<0.01);compared with APOE3+ IL-1α+TNF+Cq1 group,the expression level of Bcl-2 protein in the cells in APOE4+IL-1α+TNF+ Cq1 group was decreased(P<0.01),and the expression level of Caspase-3 protein was increased(P<0.05).Conclusion:The APOE4 genotype has a stronger ability to induce the inflammatory factors compared with APOE3;it can lead to a neurotoxicity-reactive astrocyte phenotype,increase the neurotoxicity,affect the astrocyte apoptosis,and aggravate the neuron damage.

Progress on gene polymorphism of allergic asthma / 国际儿科学杂志

Allergic asthma is a complex，polygenic disease characterized by chronic inflammation and airway hyperresponsiveness. Fungus and dust mites are the most important inhaled allergens of allergic asthma，and often exist in the form of mixed allergens. In recent years，genetic studies have shown that several genes are associated with allergic asthma attacks. This article reviews the studies on the genes related to allergic asthma caused by dust mites and fungus，such as a disintegrin and metalloproteinase 33（ADAM33），interleukin-4（IL-4），glycoprotein A repetitions predominant（GARP），toll like receptor 3（TLR3），mannose-binding lectin 2（MBL2），chemokine（C-C motif）ligand 17（CCL17）and other genes .

Correlation between gene polymorphisms of coagulation factor Ⅻ rs1801020 and resistin rs1862513 and unexplained recurrent spontaneous abortion / 国际检验医学杂志

Objective To investigate the correlation between gene polymorphisms of coagulation factor Ⅻ(FⅫ)rs1801020 and resistin rs1862513 and unexplained recurrent spontaneous abortion(URSA).Methods A total of 189 patients diagnosed with URSA and 191 healthy postpartum women during the same period were selected from the obstetric clinic of Changning Maternity and Infant Health Hospital from January 2020 to December 2022.The probe PCR was used to detect gene polymorphisms of rs1801020 and rs1862513 in peripheral blood,and the differences in genotype distribution between the groups were observed.Results The frequencies of geno-types and alleles for F Ⅻ rs1801020 in the URSA-A group were 4.9％(CC),35.7％(CT),59.5％(TT),22.7％(C),and 77.3％(T),respectively.In the control A group,the frequencies were 8.0％(CC),47.1％(CT),44.9％(TT),31.5％(C)and 68.5％(T).The frequencies of genotypes and alleles for resistin rs1862513 in the URSA-B group were 11.3％(CC),47.3％(CG),41.4％(GG),34.9％(C)and 65.1％(G).In the control B group,the frequencies were 10.2％(CC),34.1％(CG),55.7％(GG),27.3％(C)and 72.7％(G).There was no significant difference in genotype frequency of the two loci(P＞0.05),but there was a sig-nificant difference in allele frequency(P＜0.05).The distribution frequency of F Ⅻ rs1801020 T allele in the URSA group was higher than that in the control group(X2=6.32,OR=1.567,95％CI:1.100-2.238,P=0.012).The distribution frequency of resistin rs1862513 G allele in URSA group was lower than that in con-trol group(X2=4.96,OR=1.433,95％CI:1.050-1.969,P=0.026).The mutation of F Ⅻ rs1801020 C to T was a risk factor for the occurrence of URSA,while the mutation of rs1862513 C to G was a protective factor for the occurrence of URSA(P＜0.05).The combined genotype analysis showed that compared to the popu-lation carrying the rs1801020 CC+rs1862513 CC genotype combination,the population carrying the rs1801020 TT+rs1862513 CG genotype had a significantly higher risk of URSA(OR=5.684,95％CI:1.210-30.920,P=0.035).Conclusion FⅫ rs1801020 T allele may increase the risk of URSA and resistin rs1862513 G al-lele may the risk of URSA.People with rs1801020 TT+rs1862513 CG genotype combination is more likely to develop URSA than those with rs1801020 CC+rs1862513 CC genotype combination.

Gene polymorphisms of CYP2C19,MTHFR,SLCO1B1 and APOE in acute cerebral infarction patients / 国际检验医学杂志

Objective To explore the distribution of CYP2C19,MTHFR,SLCO1B1,and APOE gene poly-morphisms in patients with acute cerebral infarction,so as to provide theoretical basis for individualized drug treatment.Methods A total of 400 patients with acute cerebral infarction admitted to the hospital from 2020 to 2022 were selected as the research subjects,and the polymorphisms of CYP2C19,MTHFR,SLCO1B1 and APOE genes were tested by PCR fluorescene probe method,and the polymorphism distribution of those genes was analyzed.Results In patients with acute cerebral infarction,44.25％of CYP2C19 gene phenotype were EM type,and 9.75％of CYP2C19 gene phenotype were PM type.The proportion of mutations at the C677T locus of the MTHFR gene(CT type+TT type)was 78.50％,CC type accounted for 21.50％.78.75％of the SLCO1B1 genotypes were type Ⅰ wild type,and 1.50％SLCO1B1 gene phenotypes were type Ⅲ homozygous mutant type.The E2 and E3 types accounted for 84.25％of the APOE gene phenotype,while the E4 type ac-counted for 15.75％.Conclusion The distribution of CYP2C19,MTHFR,SLCO1B1 and APOE gene poly-morphisms in 400 acute cerebral infarction patients is analyzed,providing data support for guiding individual-ized medication in the population of acute cerebral infarction patients and of great significance for achieving safe medication.

Relationship between haptoglobin gene polymorphism and disease severity and susceptibility in senile vascular dementia patients / 国际检验医学杂志

Objective To explore the relationship between haptoglobin gene polymorphism and disease se-verity and susceptibility in senile vascular dementia patients.Methods A total of 80 patients with senile vas-cular dementia admitted to the hospital from February 2018 to February 2023 were selected as the vascular de-mentia group,and 80 stroke patients with non-vascular dementia admitted to the hospital during the same pe-riod were selected as the control group.The genotype distribution and allele frequency of haptoglobin gene were measured using polymerase chain reaction with sequence-specific primers,and their relationship with the severity and susceptibility of vascular dementia patients was analyzed.Results The proportion of history of hyperlipidemia and diabetes mellitus and the levels of total cholesterol and triglyceride in vascular dementia group were higher than those in control group,the differences were statistically significant(P＜0.05).The distribution of genotypes was in Hardy-Weinberg equilibrium(P＞0.05).The frequency of haptoglobin 2-2 genotype and haptoglobin 2 allele in vascular dementia group were higher than those in control group,and the differences were statistically significant(P＜0.05).There were significant differences in the scores of mini-mental state examination and hachinski ischaemic score among patients with vascular dementia with different haptoglobin genotypes(P＜0.05).Multivariate Logistic regression analysis showed that the carrier of hapto-globin 2-2 genotype and the carrier of haptoglobin 2 allele were independent risk factors for vascular dementia(P＜0.05).Conclusion Haptoglobin 2-2 genotype and haptoglobin 2 allele distribution frequency are associ-ated with the occurrence of vascular dementia after stroke,and those with high frequency of haptoglobin 2-2 genotype and haptoglobin 2 allele distribution suffer a severe disease,which can provide reference for early i-dentification and assessment of vascular dementia.

Correlation of FSHR gene polymorphism,BMI and sex hormone six with the risk of polycystic ovary syndrome / 解放军医学杂志

Objective To investigate the association between body mass index(BMI),sex hormone and single nucleotide polymorphisms(SNPs)of follicle-stimulating hormone receptor(FSHR)gene rs2268361 and rs2349415 and its correlation with the risk of polycystic ovary syndrome(PCOS).Methods Peripheral blood was collected from 213 PCOS patients and 207 healthy controls,attending the Department of Reproductive Medicine at the First Hospital of Shanxi Medical University,and 32 follicular fluids were randomly collected from each of the PCOS and control groups from March to August 2021.Calculation of BMI of the PCOS and control groups;The levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),testosterone(T),progesterone(P)and prolactin(PRL)in peripheral blood of the two groups were detected by immunochemiluminescence method.Polymerase chain reaction(PCR)and high-resolution melting curve(HRM)were used to analyze the polymorphisms of rs2268361 and rs2349415 in FSHR of the two groups.Quantitative real-time PCR was used to detect the expression of FSHR gene mRNA in peripheral blood and ovarian granulosa cells.Results There was a strong positive correlation between LH and LH/FSH(r=0.88,P<0.05);The levels of BMI,E2,LH,LH/FSH and T in PCOS group were significantly higher than those in control group(P<0.05);FSH level was significantly lower than that of control group(P<0.001).HRM analysis showed the frequencies of CC,CT and TT genotypes at rs2349415 were 55.9%,34.3%and 9.8%in PCOS group and 68.6%,23.2%and 8.2%in control group,respectively.The frequencies of C and T alleles were 73.0%and 27.0%in PCOS group and 80.2%and 19.8%in control group,respectively.There were significant differences in genotype frequencies and allele frequencies between the two groups(P<0.05);The expression level of FSHR mRNA was higher in ovarian granulosa cells in PCOS group than in control group(P=0.004),the expression level of FSHR mRNA in rs2349415 TT genotype was higher than that in CC(P=0.002)and CT(P=0.035)genotype.Conclusion High levels of BMI, LH, E2 and T allele of rs2349415 increased the risk of PCOS.

Association between ELL2 polymorphism and susceptibility to pleomorphic adenoma of salivary gland / 解放军医学杂志

Objective To analyze the correlation between the ELL2 gene 1119 T>C polymorphism and the susceptibility to pleomorphic adenoma of the salivary gland.Methods The pedigree of the pleomorphic adenoma family of salivary gland was drawn.The exons of ELL2 gene in 5 members of salivary pleomorphic adenoma family were sequenced.A case-control study was conducted.One hundred and twelve patients with pleomorphic adenoma of the salivary gland who visited the Department of Oral and Maxillofacial Surgery of Shanxi Bethune Hospital from January 2016 to July 2020 were taken as case group,and 176 healthy examinees from January 2019 to January 2020 were taken as control group with age and sex as matching conditions.The 1119 T>C polymorphism of ELL2 genes in the two groups were detected with high resolution melting(HRM)curve.Chi-square test was adopted to analyze the correlation between gene polymorphism and the occurrence of pleomorphic adenoma of the salivary gland,stratified analysis was performed to evaluate the synergistic effect of smoking and genotype,and real time quantitative reverse transcription polymerase chain reaction(RT-PCR)was used to detect the expression level of ELL2 in individuals with different genotypes.Results The 1119 T>C polymorphism site existed in the exon 8 of ELL2 gene in a family with pleomorphic adenoma of salivary gland.The results of case-control study showed that the genotype frequency of homozygous CC was significantly higher in patients with pleomorphic adenoma of salivary gland than that in the controls(24.1%vs.11.9%,P=0.002).Homozygous CC was associated with increased risk for developing pleomorphic adenoma of salivary gland(OR=3.059,95%CI 1.494-6.263)in this cohort.Stratification analysis showed that smoking and 1119C allele cooperated to increase the risk of pleomorphic adenoma of salivary gland(OR=3.200,95%CI 1.460-7.014).The expression level of ELL2 mRNA in CC genotype was significantly higher than that in individuals with CT or TT genotype(P<0.05).Conclusion The genetic variation of ELL2 may play an important role in the occurrence of pleomorphic adenoma of salivary gland,and smoking combined with the 1119C allele increased the risk of this disease.