Dental pain report in children and genetic polymorphism (rs4818) in Catechol-O-Methyltransferase (COMT) gene: a cross- sectional study

Abstract Aim: Polymorphisms in the COMT gene can alter enzymatic functions, raising levels of endogenous catecholamines, which stimulates beta-adrenergic receptors related to pain. This study aimed to evaluate whether a polymorphism in the COMT gene (rs4818) is associated with dental pain in children. Methodology: A cross-sectional study was conducted with a representative sample of 731 pairs of children and parents randomly selected from a population-based sample of eight-year-old children. Reports of dental pain was evaluated using a question directed at the parents and self-reported pain using the Faces Pain Scale - Revised. Dental caries experience was determined using the Decayed, Missing, and Filled Teeth (DMFT) index. For genetic analysis, DNA was obtained from oral mucosa epithelial cells of 352 children randomly selected from the initial sample. Results: Children with the CC genotype had higher odds of reporting moderate to intense pain than those with the GG genotype (OR=3.60; 95% CI=0.80-16.20; p=0.03). These same children had greater odds of parental reports of pain (OR=1.93; 95% CI=0.91-4.08; p=0.02). Moreover, lower schooling of parents/guardians and caries experience in the primary dentition were significantly associated with greater odds of a parental report of dental pain (OR=2.06; 95% CI=1.47-2.91; p<0.001; OR=6.26; 95% CI=4.46-8.78; p<0.001). Conclusions: The rs4818 polymorphism of the COMT gene is associated with dental pain. Children with the C allele are more likely to report higher levels of pain. Clinical Relevance: Even though the experience of pain is subjective and multifactorial, this study raises the hypothesis that there is a genetic predisposition to dental pain that should be considered in clinical practice.

Influence of genetic polymorphisms on oral health-related quality of life after root canal treatment

Abstract To evaluate the impact of genetic polymorphisms in interleukins (IL1A rs17561, rs1304037; IL10 rs1800871; IL1RN rs9005), nitric oxide (NOS2 rs2779249, rs2897518) and suppressor of cytokine signaling (SOCS1 rs243327, rs33977706) on oral health-related quality of life (OHRQoL) of patients under-going root canal treatment (RCT). Methods: The sample consisted of 108 participants, presenting single-rooted teeth with asymptomatic periapical periodontitis. The impact of the OHRQoL was recorded using the Oral Health Impact Profile (OHIP-14) before, seven, and 30 days after RCT. Saliva samples were collected as a source of genomic DNA. Genetic polymorphisms were genotyped by Real-Time PCR using the Taqman method. Univariate and Multivariate analyses were used (p<0.05). Results: A significant difference was observed for the polymorphism rs2297518 in the NOS2 gene in functional limitation in the codominant (p=0.037) and recessive (p=0.001) models; in the physical pain (p<0.001 in both models); in psychological discomfort (p<0.001 in both models); in physical disability (p<0.001 in both models) and in psychological disability (p<0.001 in both models). Polymorphisms in the SOCS1 gene, in the recessive model, rs33977706 (p=0.045) and rs243327 (p=0.019), influenced the OHRQoL in the psychological discomfort domain. Conclusions: Polymorphisms in NOS2 and SOCS1 genes influenced the OHRQoL of patients undergoing RCT.

Resumo Avaliar o impacto de polimorfismos genéticos em interleucinas (IL1A rs17561, rs1304037; IL10 rs1800871; IL1RN rs9005), óxido nítrico (NOS2 rs2779249, rs2897518) e supressor da sinalização de citocinas (SOCS1 rs243327, rs33977706) na qualidade de vida relacionada à saúde bucal (QVRSB) de pacientes submetidos a tratamento endodôntico (TE). Métodos: A amostra foi composta por 108 participantes, que apresentavam dentes unirradiculares com lesão periapical assintomática. O impacto da QVRSB foi registrado usando o Oral Health Impact Profile (OHIP-14) antes, sete e 30 dias após o TE. Amostras de saliva foram coletadas como fonte de DNA genômico. Os polimorfismos genéticos foram genotipados por PCR em tempo real usando o método Taqman. Análises univariadas e multivariadas foram utilizadas (p<0,05). Resultados: Observou-se diferença significativa para o polimorfismo rs2297518 no gene NOS2 na limitação funcional nos modelos codominante (p=0,037) e recessivo (p=0,001); na dor física (p<0,001 em ambos os modelos); no desconforto psicológico (p<0,001 em ambos os modelos); na deficiência física (p<0,001 em ambos os modelos) e na deficiência psicológica (p<0,001 em ambos os modelos). Polimorfismos no gene SOCS1, no modelo recessivo, rs33977706 (p=0,045) e rs243327 (p=0,019), influenciaram a QVRSB no domínio desconforto psicológico. Conclusões: Polimorfismos nos genes NOS2 e SOCS1 influenciaram a QVRSB de pacientes submetidos a TE.

Genetic polymorphism of interleukins 6 and 17 correlated with apical periodontitis: A Cross-sectional study

Abstract Interleukins 6 and 17 act in bone resorption in the presence of infections of endodontic origin for host defense. Genetic polymorphisms may be associated with increased bone loss, represented by areas of large periapical lesions. This study aimed to verify the frequency of interleukin 6 and 17 gene polymorphism in patients with asymptomatic apical periodontitis or chronic apical abscess and to verify the existence of correlations between periapical lesion area with age, gender, and presence of the polymorphism, in the studied population, in the state of Pernambuco. A population consisting of thirty diagnosed individuals was included. The area of the lesions was measured in mm². Genomic DNA was extracted and genotyping was performed by Polymerase Chain Reaction Restriction Fragment Length Polymorphism for interleukin 6 (rs 1800795) and interleukin 17 (rs 2275913). Fisher's exact, chi-square, and odds ratio tests were used. A logistic regression analysis was also performed using sex, age, and the presence of polymorphism as covariates, in addition to linear regression to test the relationship between age and lesion area. All tests used a significance level of 0.05% (p ≤0.05%). There was no statistical significance in the occurrence of large areas of periapical lesions correlated with age, sex, and diagnosis, nor in the distribution of alleles in the polymorphism of interleukins 6 and 17 in the studied groups. The frequency of homozygous and heterozygous polymorphism was high. The polymorphism of these interleukins is not correlated with the increase in the areas of asymptomatic periapical inflammatory lesions.

Resumo As interleucinas 6 e 17 atuam na reabsorção óssea na presença de infecções de oriegem endodôntica para defesa do hospedeiro. Polimorfismos genéticos podem estar associados ao aumento da perda óssea, representada por áreas de lesões periapicais grandes. O objetivo deste estudo foi verificar a frequência do polimorfismo dos genes interleucina 6 e 17 em pacientes com periodontite apical assintomática ou abscesso apical crônico e verificar a existência de correlações entre área de lesão periapical com idade, sexo e presença do polimorfismo, na população estudada, no estado de Pernambuco. Foi incluída uma população constituída por trinta indivíduos diagnosticados. A áreas da lesões foram medidas em mm². O DNA genômico foi extraído e a genotipagem realizada por Polimorfismo de Comprimento de Fragmento de Restrição de Reação em Cadeia da Polimerase para interleucina 6 (rs 1800795) e interleucina 17 (rs 2275913). Os testes exato de Fisher, qui-quadrado e odds ratio foram utilizados. Uma análise de regressão logística também foi realizada usando sexo, idade e presença de polimorfismo como covariável, além de regressão linear para testar a relação da idade e área da lesão. Todos os testes utilizaram um nível de significância de 0,05% (p ≤0.05%). Não houve significância estatística na ocorrência das áreas grandes de lesões periapicais correlacionadas com idade, sexo e diagnóstico nem nas distribuições de alelos no polimorfismo das interleucinas 6 e 17 nos grupos estudados. A frequência de polimorfismo homozigoto e heterozigoto foi alta. O polimorfismo dessas interleucinas não está correlacionado ao aumento das áreas das lesões inflamatórias periapicais assintomáticas.

Research Progress on Genetic Susceptibility to Triple-Negative Breast Cancer / 肿瘤防治研究

Triple-negative breast cancer (TNBC) is a type of breast cancer that is difficult to treat, has a poor prognosis, and is prone to recurrence and metastasis in the early postoperative period. The age of patients is tending younger, and the racial difference is large. It is also related to family history, and genetic susceptibility is obvious. So, elucidating the genetic risk factors of TNBC and obtaining precise therapeutic targets are urgent tasks. Obtaining reliable characteristic genes and their polymorphisms between TNBC of different subtypes is difficult. This review summarizes the susceptibility genes and the polymorphisms of TNBC susceptibility genes of different molecular subtypes, in order to develop effective TNBC prevention strategies and find effective therapeutic targets. This review provides a theoretical basis for promoting the study of TNBC from the perspective of genetics.

Quantitative assessment of the relevance of organic-anion-transporting-polypeptide 1B1 and 2B1 polymorphisms in fexofenadine pharmacokinetic variants via pharmacometrics / 药物分析学报

Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmaco-kinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic variability.Polymorphisms of the organic-anion-transporting-polypeptide(OATP)1B1 and 2B1 have been proposed to be closely related to fexofenadine pharmacokinetic diversity.Therefore,modeling was performed using fexofenadine oral exposure data according to the OATP1B1-and 2B1-polymorphisms.OATP1B1 and 2B1 were identified as effective covariates of clearance(CL/F)and distribution volume(V/F)-CL/F,respectively,in fexofenadine pharmacokinetic variability.CL/F and average steady-state plasma con-centration of fexofenadine differed by up to 2.17-and 2.20-folds,respectively,depending on the OATP1B1 polymorphism.Among the individuals with different OATP2B1 polymorphisms,the CL/F and V/F differed by up to 1.73-and 2.00-folds,respectively.Ratio of the areas under the curves following single-and multiple-administrations,and the cumulative ratio were significantly different between OATP1B1-and 2B1-polymorphism groups.Based on quantitative prediction comparison through a model-based approach,OATP1B1 was confirmed to be relatively more important than 2B1 regarding the degree of effect on fexofenadine pharmacokinetic variability.Based on the established pharmacokinetic-pharmacodynamic relationship,the difference in fexofenadine efficacy according to genetic poly-morphisms of OATP1B1 and 2B1 was 1.25-and 0.87-times,respectively,and genetic consideration of OATP1B1 was expected to be important in the pharmacodynamics area as well.This population phar-macometrics study will be a very useful starting point for fexofenadine precision medicine.

Correlation of maternal drug use and cytochrome P450 geneticpolymorphisms with congenital heart disease in offspring / 西安交通大学学报(医学版)

【Objective】 To investigate the association of maternal medication during early pregnancy and cytochrome P450 (CYP450) genetic polymorphisms with the risk of congenital heart disease (CHD) in offspring. 【Methods】 We selected 127 pregnant women with CHD fetuses as the observation group and 132 pregnant women with non-CHD fetuses as the control group. Their characteristics and medication history were investigated, and CYP450 polymorphisms were detected. Logistic regression analysis was used to assess the association between maternal medication, CYP450 gene variations, and offspring CHD risk. 【Results】 The risk of CHD in offspring was higher in the observation group with maternal use of ovulation induction drugs, antihypertensive drugs, antibiotics, antidepressants, miscarriage prevention drugs, and traditional Chinese medicine (P<0.05). The A/T and T/T genotypes in rs1065852 and the C/G and G/G genotypes in rs16947 increased the risk of CHD in offspring compared to their respective genotypes. The risk of CHDs in offspring increased with the presence of risk genotypes (A/T or T/T) at the rs1065852 locus of the maternal CYP450 gene and early pregnancy medication use (P<0.05); the same was observed for risk genotypes (C/G or G/G) at the rs16947 locus (P<0.05). 【Conclusion】 Maternal medication during early pregnancy may be associated with offspring CHD, and the rs1065852 and rs16947 loci of CYP450 are significantly related to the risk of CHD in offspring.

Distribution of rs8022522 and rs12894524 polymorphisms of miR-208 gene in Guangxi population / 西安交通大学学报(医学版)

【Objective】 To explore the distribution of polymorphisms of miR-208 genes rs8022522 and rs12894524 locus in Guangxi healthy population and compare the differences in the polymorphism distribution in different population. 【Methods】 SNPscan technology was used to detect genotypes of rs8022522 and rs12894524 from 297 healthy people in Guangxi, and the results were compared with other populations from Human genome Haplotype Map(HapMap) data. 【Results】 Three genotypes, namely, AA (2.7%), AG (24.2%) and GG (73.1%), in rs8022522 were found, with the allele frequencies of A and G being 14.8% and 85.2%. The genotypes of rs12894524 locus were TT (1.3%), TG (13.5%) and GG (85.2%), and the frequency of T and G allele was 8.1% and 91.9%, respectively. rs8022522 and rs12894524 locus genotypes and allele frequencies were significantly different from HapMap-CEU, HapMap- YRI and HapMap-TSI (P<0.05). Compared with HapMap-JPT and HapMap-CHB, there was no significant difference in genotype or allele frequency between the two sites (P>0.05). As for the blood lipid level among the three genotypes in rs8022522, the level of high density lipoprotein cholesterol (HDL-C) with GG genotype was significantly different from that in AG group (P<0.05). 【Conclusion】 The polymorphisms of rs8022522 and rs12894524 of miR-208 gene in Guangxi population are different from those in other regions to varying degrees. The polymorphism of rs8022522 locus is related to the level of HDL-C.

Associations of genetic variants in M3 receptor with blood pressure responses to salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 M3 muscarinic acetylcholine receptor(M3 receptor), encoded by CHRM3 gene, is widely distributed in the cardiovascular system and plays an important role in cardiac regulation. The aim of this study was to assess the association of genetic variants in M3 receptor with blood pressure(BP) responses to controlled dietary sodium and potassium interventions. 【Methods】 A total of 333 subjects from 124 families were recruited from the rural areas of northern China. After a three-day baseline observation, they were sequentially on a seven-day low-salt diet, a seven-day high-salt diet, and a seven-day high-salt diet plus potassium supplementation. Thirteen CHRM3 single nucleotide polymorphisms(SNPs) were selected for analysis. 【Results】 SNP rs10802811 of the CHRM3 was significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to both low-salt and high-salt diets while SNPs rs6429147, rs373288072, rs114677844 and rs663148 showed significant associations with systolic BP(SBP) and MAP responses to high-salt diet. In addition, SNP rs6692904 was significantly associated with SBP, DBP and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in M3 receptor are significantly associated with BP responses to sodium and potassium intervention, suggesting that M3 receptor may be mechanistically involved in BP salt and potassium sensitivity.

Association of genetic variants in uromodulin with blood pressure responses to dietary salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we aimed to examine the association of genetic variants in uromodulin with blood pressure(BP) responses to dietary interventions of sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Mei County, Shaanxi Province, were recruited to establish the salt-sensitive hypertension study cohort. Among them, 333 non-parent subjects were selected and sequentially maintained on a normal-diet for 3 days, low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Thirteen single nucleotide polymorphisms(SNPs) in the uromodulin gene were genotyped on the MassARRAY platform. 【Results】 BP levels decreased from the baseline to low-salt diet, increased from low-salt to high-salt diet, and decreased again from the high-salt diet to the high-salt plus potassium supplementation intervention. SNPs rs77875418 and rs4997081 of the uromodulin gene were significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to high-salt diet. In addition, SNPs rs77875418, rs79245268, rs4293393, rs6497476, rs4997081, rs13333226, and rs12917707 were significantly associated with systolic BP(SBP), DBP, and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in uromodulin gene are significantly associated with BP responses to sodium and potassium supplementation, suggesting that uromodulin may be mechanistically involved in BP sodium-sensitivity and potassium-sensitivity.

Association of genetic variants in NEDD4L with blood pressure responses to dietary salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 4-like protein with down-regulated expression and development in neural precursor cells (NEDD4L) plays an important role in blood pressure (BP) regulation and sodium homeostasis by regulating epithelial sodium channel protein. In this study, we aimed to explore the relationship of NEDD4L gene polymorphisms with BP responses to sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Meixian County, Shaanxi Province, were recruited to establish a salt-sensitive hypertension study cohort. All the subjects received a 3-day baseline survey, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Their BP was measured and peripheral blood samples were collected at different intervention periods. The 14 gene polymorphisms of NEDD4L gene were genotyped and analyzed by MassARRAY platform. 【Results】 BP decreased on a low-salt diet, and significantly increased on a high-salt diet, and decreased again after potassium supplementation. NEDD4L SNPs rs74408486 were significantly associated with systolic BP, diastolic BP and mean arterial pressure responses to the low-salt diet. SNPs rs292449 and rs2288775 were significantly associated with pulse pressure response to the high-salt diet. In addition, SNPs rs563283 and rs292449 were significantly associated with diastolic BP, mean arterial pressure, and pulse pressure responses to high-salt and potassium supplementation diet. 【Conclusion】 NEDD4L gene polymorphisms were significantly associated with BP responses to sodium and potassium intake, suggesting that NEDD4L gene may be involved in the development of salt sensitivity and potassium sensitivity.

Associations of genetic polymorphisms in Corin with blood pressure responses to salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 Corin, a transmembrane serine protease that can cleave atrial natriuretic peptide precursor (pro-ANP) into atrial natriuretic peptide with smaller bioactive molecules, participates in the pathophysiological process of hypertension and cardiac hypertrophy. The purpose of this study was to explore the relationship of Corin gene variation with blood pressure responses to sodium and potassium dietary interventions. 【Methods】 In 2004, we recruited 514 participants from 124 families in 7 villages of Baoji, Shaanxi Province, China. All the subjects received a 3-day normal diet, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Fifteen single nucleotide polymorphisms (SNPs) of Corin gene were selected for final analysis. 【Results】 SNPs rs12509275 were significantly associated with diastolic blood pressure (DBP) response to low-salt diet, while rs3749584 was associated with pulse pressure (PP) response to low-salt diet.SNP rs3749584 and rs10517195 were significantly associated with PP response to high-salt diet. In addition,rs17654278 were significantly associated with systolic blood pressure (SBP) response to high-salt and potassium supplementation, rs2271037 was significantly correlated with DBP responses to high-salt and potassium supplementation, and rs4695253, rs12509275, rs2351783, rs36090894 were significantly associated with PP response to high-salt and potassium supplementation. 【Conclusion】 Corin gene polymorphisms were associated with blood pressure response to sodium and potassium, suggesting that Corin gene may be involved in pathophysiological process of salt sensitivity and potassium sensitivity.

The challenge of finding Chinese blood groups / 中国输血杂志

Up to now, hundreds of human blood groups have been detected globally, but none have been found in the Chinese population. China is a multi-ethnic country with rich genetic polymorphism and variation. The Chinese pangenome reference reveals that the Chinese carry some genetic variations that are different from other ethnic groups in the world, especially the discovery of approximately 5 million new base pair sequences, which are considered the core genome sequences of the Chinese population. Research on red blood cell membrane proteomics has shown that red blood cells carry over 2 600 kinds of erythrocyte membrane proteins, and currently only 37 protein molecules have detected blood group antigens. The above data suggest that the possibility of new blood group in the Chinese population cannot be ruled out. This comment describes the history of the discovery of blood groups and the challenges faced by Chinese scholars.

Analysis of pretreatment drug resistance and polymorphic sites in CRF08_BC strains among HIV-1 patients / 中华微生物学和免疫学杂志

Objective:To investigate the prevalence of pretreatment drug resistance and the genetic polymorphism of CRF08_BC strains among HIV-1 patients in China.Methods:This cross-sectional survey involved the plasma samples of HIV patients in a national pretreatment HIV drug resistance survey conducted in 2018. RNA was extracted from the samples. The fragments containing protease and partial reverse transcriptase (PR/RT) regions were obtained and sequenced. Drug resistance was analyzed using Stanford HIVdb Program. Differences in polymorphic mutations between drug-resistant and non-drug-resistant HIV-1 strains were analyzed by Chi-square test or Fisher′s exact test. The association between drug-resistant and polymorphic mutations was evaluated using CorMut R package. Molecular transmission networks were constructed using HIV-TRACE software. Results:Totally 465 partial pol sequences were obtained from individuals with CRF08_BC infection in 25 provinces and cities. The total pretreatment drug resistance rate was 17.8% (83/465). The pretreatment drug resistance rates to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) were 16.6% (77/465), 1.1% (5/465) and 0.9% (4/465), respectively. The resistance rate to rilpivirine (RPV) was the highest (15.7%, 73/465). The most common mutation was E138A (11.6%, 54/465). There were six polymorphic mutations (S162C, K102Q, T200A, V179E, I202V, T200M) that co-variated with E138A. The molecular transmission network showed that patients infected with CRF08_BC strains carrying the resistant mutations at position E138 mainly gathered in clusters in Yunnan and Sichuan, and the highest degree of connection was in Lincang, Yunnan. Conclusions:In China, HIV-1 CRF08_BC-infected patients showed a high rate of pretreatment resistance to one of the second-generation NNRTIs, namely RPV. Further researches were warranted to evaluate the impacts of co-mutations of the E138A mutation and polymorphic sites on HIV resistance and replicative capacity.

Association of Tumor Necrosis Factor-α (-G308A) Polymorphism with risk of Upper Gastrointestinal Bleeding from Schistosomiasis in Pernambuco

ABSTRACT Background: We evaluated the association between polymorphisms in the tumor necrosis factor alpha (TNF-α) (-G308A) gene and upper gastrointestinal bleeding (UGIB) in schistosomiasis. Methods: This was a transverse study involving 294 Brazilian patients infected with Schistosoma mansoni. Results: The homozygous A/A genotype in TNF-α (-G308A) showed a risk association (prevalence ratio = 1.90, p = 0.008) with UGIB. There was no statistically significant difference in serum TNF-α levels between the clinical groups. Conclusions: The polymorphic TNF-α (-G308A) can be a risk factor for UGIB, in addition to being a potentially predictive factor for the severity of UGIB in schistosomiasis.

Temporomandibular disorder in construction workers associated with ANKK1 and DRD2 genes

Abstract The study aimed to explore the influence of genetic polymorphisms in ANKK1 and DRD2 on the signs and symptoms of temporomandibular disorder (TMD) in construction workers. This cross-sectional study included only male subjects. All construction workers were healthy and over 18 years age. Illiterate workers and functionally illiterate workers were excluded. The diagnosis of TMD was established according to the Research Diagnostic Criteria for TMD (RDC/TMD). Genomic DNA was used to evaluate the genetic polymorphisms ANKK1 (rs1800497) and DRD2 (rs6275; rs6276) using Real-Time PCR. Chi-square or Fisher exact tests were used to evaluate genotypes and allele distribution among the studied phenotypes. The established alpha of this study was 5%. The sample included a total of 115 patients. The age of the patients ranged from 19 to 70 years (mean age 38.2; standard deviation 11.7). Chronic pain (87.7%), disc displacement (38.2%), and joint inflammation (26.9%) were the most frequently observed signs and symptoms. The genetic polymorphism rs6276 in DRD2 was associated with chronic pain (p=0.033). In conclusion, our study suggests that genetic polymorphisms in DRD2 and ANKK1 may influence TMD signs and symptoms in a group of male construction workers.

Resumo O objetivo do estudo foi explorar a influência de polimorfismos genéticos em ANKK1 e DRD2 sobre os sinais e sintomas da disfunção temporomandibular (DTM) em trabalhadores da construção civil. Este estudo transversal incluiu apenas indivíduos do sexo masculino. Todos os trabalhadores da construção civil eram saudáveis ​​e maiores de 18 anos. Foram excluídos os trabalhadores analfabetos e analfabetos funcionais. O diagnóstico de DTM foi estabelecido de acordo com o Research Diagnostic Criteria para DTM (RDC/TMD). O DNA genômico foi usado para avaliar os polimorfismos genéticos ANKK1 (rs1800497) e DRD2 (rs6275; rs6276) usando PCR em tempo real. Testes qui-quadrado ou exato de Fisher foram utilizados para avaliar genótipos e distribuição de alelos entre os fenótipos estudados. O alfa estabelecido deste estudo foi de 5%. A amostra incluiu um total de 115 pacientes. A idade dos pacientes variou de 19 a 70 anos (média de idade 38,2; desvio padrão 11,7). Dor crônica (87,7%), deslocamento de disco (38,2%) e inflamação articular (26,9%) foram os sinais e sintomas mais observados. O polimorfismo genético rs6276 em DRD2 foi associado a dor crônica (p=0,033). Em conclusão, nosso estudo sugere que polimorfismos genéticos em DRD2 e ANKK1 podem influenciar sinais e sintomas de DTM em um grupo de trabalhadores da construção civil do sexo masculino.

O papel dos polimorfismos genéticos na etiologia da endometriose / The role of genetic polymorphism in the etiology of endometriosis

O objetivo deste estudo é apresentar uma revisão atualizada sobre o papel dos polimorfismos genéticos na etiologia da endometriose. Trata-se de uma pesquisa bibliográfica feita no PubMed utilizando os descritores "polymorphism and endometriosis". Foram identificados 36 artigos e após aplicação dos critérios de inclusão foram selecionados 17 artigos para a amostra final. Os principais resultados foram: 1) cerca de 60% dos artigos foram publicados em 2019; 2) em 35,3% dos estudos o número de casos e controles investigados foi menor que 100; 3) a maioria dos trabalhos investigou de um a dois polimorfismos por gene; 4) a produção científica sobre endometriose é maior em países orientais; 5) houve heterogeneidade quanto aos periódicos onde os trabalhos foram publicados; 6) as principais técnicas para detecção de polimorfismos foi a PCR-RFLP e o PCR em tempo real, com frequências semelhantes. Em suma, os polimorfismos genéticos podem estar implicados na etiologia da endometriose.

The aim of this study is to present an updated review on the role of genetic polymorphisms in the etiology of endometriosis. This is a literature review made on PubMed using the descriptors "polymorphism and endometriosis". A total 36 articles were identified and, after applying the inclusion criteria, 17 articles were selected for the final sample. The main results were: 1) approximately 60% of the articles were published in 2019; 2) 35.3% of the studies investigated less than 100 cases and controls; 3) most studies investigated one to two polymorphisms per gene; 4) scientific production on endometriosis is higher in Eastern countries; 5) heterogeneity was observed regarding the journals where works were published; 6) the main techniques for detecting polymorphisms were PCR-RFLP and real-time PCR, with similar frequencies. In summary, it can be concluded that genetic polymorphisms may be implicated in the etiology of endometriosis.

Evaluation of the g473a polymorphism in the lysyl oxidase gene as a risk factor related to the occurrence of breast cancer in Brazilian women / Avaliação do polimorfismo g473a no gene da lisil oxidase como fator de risco relacionado à ocorrência de câncer de mama em mulheres brasileiras

Introdução: o câncer de mama é o tipo de câncer mais diagnosticado e a principal causa de morte entre as mulheres em todo o mundo. Aproximadamente 1,67 milhões de novos casos de câncer de mama foram diagnosticados em 2012, levando a mais de meio milhão de mortes. O câncer de mama foi responsável por 11,6% dos novos casos de cânceres diagnosticados (2.089 milhões) e 9,2% (787.000) das mortes relacionadas ao câncer para ambos os sexos e em todas as idades em todo o mundo em 2018.Objetivo: o câncer de mama como o carcinoma mais diagnosticado no mundo e a principal causa de morte entre as mulheres, é uma morbidade de grande importância, sendo o objetivo deste estudo avaliar a associação entre o polimorfismo do gene LOX G473A (rs1800449) a ocorrência de câncer de mama, potencialmente estabelecendo um novo achado na identificação de riscos, prevenção, e atendimento a um grupo específico de mulheres.Método: neste estudo de coorte retrospectivo, a frequência do polimorfismo LOX G473A foi avaliada em 148 mulheres com câncer de mama e 245 mulheres sem a doença. Todas as pacientes responderam a um questionário para identificação de possíveis fatores de risco e posteriormente realizaram coleta de sangue periférico para estudo do gene LOX. O DNA foi extraído seguido da amplificação gênica via PCR, e o polimorfismo foi estudado por eletroforese de fragmentos específicos após digestão das amostras com a endonuclease de restrição do organismo Providencia stuartii.Resultados: este estudo identificou o uso de anticoncepcional oral e o antecedente familiar de câncer de mama como fatores de risco par a doença; o polimorfismo G473A na LOX não foi identificado como fator de risco.Conclusão: não foi observada relação entre o polimorfismo LOX G473A e a ocorrência de câncer de mama.

Introduction: breast cancer is the most diagnosed type of cancer and the leading cause of death among women worldwide. Approximately 1.67 million new cases of breast cancer were diagnosed in 2012, leading to more than half a million deaths. Breast cancer accounted for 11.6% of newly diagnosed cancers (2,089 million) and 9.2% (787,000) of cancer-related deaths for both sexes and at all ages worldwide in 2018.Objective: breast cancer, as the most diagnosed carcinoma in the world and the leading cause of death among women, is a morbidity of outstanding importance, and the object of this study is to evaluate the association between the LOX gene G473A (rs1800449) polymorphism and breast cancer occurrence, potentially establishing a new finding in the identification of risks, prevention, and care for a specific group of women.Methods:in this retrospective cohort study, LOX G473A polymorphism frequency was assessed in 148 women with breast cancer and 245 women without breast cancer. All patients completed a questionnaire to identify possible risk factors and subsequently underwent peripheral blood collection to study the LOX gene. DNA was extracted followed by gene amplification via PCR, and the polymorphism was studied by specific fragment electrophoresis after digestion of the samples with the restriction endonuclease Pstl.Results: this study identified the use of oral contraceptives and family history of breast cancer as risk factors for breast cancer; the G473A polymorphism in LOX was not identified as a risk factor.Conclusion: a relationship was not observed between the LOX G473A polymorphism and the occurrence of breast cancer.

Diversidad genética de aedes aegypti en el eje transfronterizo Central-Alto Paraná en Paraguay / Genetic diversity of Aedes aegypti in the central-upper Paraná Cross-Border axis in Paraguay

RESUMEN Objetivos: Conocer la diversidad genética de Aedes aegypti en el corredor vial transfronterizo Central-Alto Paraná de Paraguay, con registros de casos de dengue. Materiales y métodos: Se seleccionaron veinte hembras adultas de la eclosión de huevos de Ae. aegypti procedentes de casas geolocalizadas en los departamentos de Alto Paraná, Caaguazú, Cordillera y Central, entre el 2018 y 2019. Se extrajo ADN del tejido de las hembras para amplificación aleatoria de sus patrones polimórficos mediante amplificación aleatoria del ADN polimórfico por PCR (RAPD-PCR), usando cebadores H3 y B03 a fin de conocer parámetros genéticos de diversidad poblacional. Las relaciones entre las poblaciones de mosquitos según la localidad fueron visualizadas mediante análisis no apareado de la media aritmética. Las áreas idóneas de distribución geográfica real y potencial de estas poblaciones de Ae. aegypti fueron analizadas mediante DIVA-GIS 7.3.0 y MAXENT. Resultados: Se identificaron 40 loci mediante perfiles RAPD-PCR, con diferenciación génica moderada (Gst = 0,12). El corredor transfronterizo presentó condiciones bioclimáticas para la presencia de poblaciones variantes de Ae. aegypti, siendo determinantes en la distribución la precipitación del trimestre más cálido y la temperatura media del trimestre más seco. Conclusiones: Se evidencia que existe diversidad genética moderada en las poblaciones de Ae. aegypti procedentes de zonas con registros de casos de dengue ubicadas en el corredor vial transfronterizo que une los departamentos Central y Alto Paraná de Paraguay. El estudio de variabilidad genética de Ae. aegypti es de gran utilidad para la vigilancia entomoepidemiológica y evaluación de posibles eventos de resistencia al control químico.

ABSTRACT Objective: To determine the genetic diversity of Aedes aegypti in the Central-Alto Paraná cross-border road corridor of Paraguay, an area that has reports of dengue cases. Materials and methods: Twenty adult females were selected from hatching Ae. aegypti eggs from households geolocated in the departments of Alto Paraná, Caaguazú, Cordillera and Central, between 2018 and 2019. DNA was extracted from the tissue of females for amplifying their polymorphic patterns by random amplification of polymorphic DNA by PCR (RAPD-PCR), using primers H3 and B03 in order to identify genetic parameters of population diversity. The relationships between mosquito populations according to locality were observed by unpaired arithmetic mean analysis. We used DIVA-GIS 7.3.0 and MAXENT to analyze the suitable areas of actual and potential geographic distribution of these Ae. aegypti populations. Results: Forty loci were identified by RAPD-PCR profiling, with moderate gene differentiation (Gst = 0.12). The cross-border corridor presented bioclimatic conditions for the presence of variant populations of Ae. aegypti, with precipitation in the warmest quarter and mean temperature in the driest quarter being determinant in the distribution. Conclusions: There is evidence of moderate genetic diversity in Ae. aegypti populations from areas that have reported dengue cases in the cross-border road corridor linking the Central and Alto Paraná departments of Paraguay. The study of genetic variability of Ae. aegypti is very useful for entomo-epidemiological surveillance and evaluation of possible resistance to chemical control.

Association of FOXO3 polymorphism (rs3800231) and clinical subphenotypes of beta thalassemic individuals

Abstract Introduction Studies have shown that the loss of the FOXO3 transcriptional function is involved in the pathophysiology of some chronic erythroid disorders, including beta-thalassemia (β-thal). Therefore, the single nucleotide polymorphism (SNP) rs3800231 (35-2764A > G) could contribute to alterations in its transcriptional activity, acting as a modifier of β-thal phenotypic manifestations. Objective and method In order to better understand the genotypic and/or allelic distributions among β-thal patients, we evaluated 83 β-thal heterozygous and 20 homozygous, compared to 117 individuals without hemoglobinopathies (control group). Additionally, we verified any influence of the FOXO3 polymorphism on clinical manifestations among β-thal homozygotes. Results We obtained higher frequencies of the wild-type homozygous (AA) and the wild-type allele (A) in the β-thal group (p< 0.0001 and p= 0.00014, respectively). The most common clinical manifestations found among β-thal homozygotes were iron overload (90%), splenomegaly (65%) and bone complications (35%), e.g., osteopenia/osteoporosis. We observed that close to 80% of the patients presenting such manifestations had the genotype AA. However, we did not find any significant involvement of the FOXO3 polymorphism in clinical manifestation occurrences. Conclusion Thus, we concluded that the SNP rs3800231 did not play a significant role as a modifier of the clinical manifestations observed in the β-thal homozygotes studied.

Estudios genéticos del metabolismo de la warfarina y su utilidad en la toma de decisiones / Genetic studies of warfarin metabolism and its usefulness in decision making

Resumen Introducción: Al momento de valorar la necesidad de realizar un reemplazo quirúrgico valvular cardiaco es posible elegir entre una válvula mecánica o una bioprotésica; la elección debe tener presentes los riesgos de la terapia anticoagulante y la necesidad potencial o el riesgo de nuevas intervenciones. La anticoagulación se realiza con antagonistas de la vitamina K, y de estos, la warfarina es el que se prescribe con mayor frecuencia. Por su metabolismo hepático (P450), dicho medicamento tiene múltiples interacciones farmacológicas y no farmacológicas que en ocasiones se convierten en un verdadero problema en la práctica clínica. Hasta la fecha no se recomienda realizar de forma rutinaria una dosificación guiada por genotipo; sin embargo, se requieren estudios genéticos para definir conductas médicas cuando se hace difícil su manejo. Caso clínico: Se describe el caso de una mujer de 37 años portadora de una válvula mitral mecánica por enfermedad reumática, anticoagulada de forma crónica con warfarina; sin embargo, durante el seguimiento tuvo múltiples consultas a urgencias (entre dos y tres veces por mes) por niveles de anticoagulación en rangos subterapéuticos, como valores elevados de INR. Presentó infarto agudo de miocardio con coronarias sanas e isquemia cerebral transitoria en contexto de INR bajo, considerados así de etiología tromboembólica. Por estas dificultades se decidió realizar la medición de los niveles de factor II de la coagulación, el cual fue normal a pesar del uso del medicamento, por lo que se sospechó resistencia al fármaco. Se solicitó estudio genético que mostró genotipo asociado con actividad enzimática reducida o normal de la CYP2C9, además un genotipo WARF CYP2C9 *1/*2 y WARF VKORC1 A/A, con lo cual se concluyó que la paciente presentaba un comportamiento metabólico divergente para warfarina. Se decidió realizar un reemplazo de válvula mecánica por válvula bioprotésica, con el objetivo de suspender el uso de la warfarina. La paciente presentó una evolución clínica satisfactoria. Conclusiones: La farmacogenética ha logrado identificar polimorfismos en los genes implicados en el metabolismo de la warfarina, los cuales están relacionados con riesgo de sangrado. Estas variantes se encuentran relacionadas con los genes CYP2C9, CYP4F2 y VKORC1. Si bien no se ha demostrado un impacto clínico en los ajustes de warfarina guiados por genotipo, dichos exámenes se hacen necesarios en algunos casos para sugerir un cambio en la dosis del medicamento o su suspensión definitiva.

Abstract Introduction: When assessing the need for a cardiac valvular surgical replacement, it is possible to choose between a mechanical or bioprosthetic valve; The choice must take into account the risks of anticoagulant therapy and the potential need and/or risk of new interventions. Anticoagulation is performed with vitamin K antagonists and warfarin is the most commonly prescribed of these. This medicine due to its hepatic metabolism (P450) has multiple pharmacological and non-pharmacological interactions that sometimes become a real problem in clinical practice. To date, it is not recommended to routinely perform a genotype-guided dosage. However, such genetic studies are necessary to define medical behaviors when handling is difficult. Case report: It is described a case of a 37-year-old woman with a mechanical mitral valve due to rheumatic disease, chronically anticoagulated with warfarin; however, during the follow-up with multiple emergency consultations (2-3 times per month) for anticoagulation levels in subtherapeutic ranges such as elevated INR levels. She presented acute myocardial infarction with healthy coronary arteries and transient cerebral ischemia in the context of low INR thus considered thromboembolic etiology. Due to these difficulties, it was decided to measure coagulation factor II levels, which was normal despite the use of the drug, suspecting drug resistance. A genetic study was requested that showed genotype associated with reduced or normal CYP2C9 enzymatic activity, plus a WARF CYP2C9 * 1/* 2 and WARF VKORC1 A/A genotype concluding that the patient presented a divergent metabolic behavior for warfarin. It was decided to perform a mechanical valve replacement with a bioprosthetic valve, in order to suspend the use of warfarin. The patient presented a satisfactory clinical evolution. Conclusions: Pharmacogenetics has managed to identify polymorphisms in the genes involved in warfarin metabolism, which are related to bleeding risk. These variants are related to the CYP2C9, CYP4F2 and VKORC1 genes. Although no clinical impact has been demonstrated in genotype-guided warfarin adjustments, such tests are necessary in some cases to suggest a change in the dose of the medication or the definitive suspension.