Association of Fibroblast Growth Factor-1 Promoter Polymorphism and its Serum Concentrations with Repeated Implantation Failure after In vitro Fertilisation: A Cross-sectional Study.

Background: Fibroblast growth factors (FGFs) play a key role in embryo implantation and support endometrial trophoblastic interaction. Aim: The aim of the study was to evaluate the association between FGF-1 (rs34011) gene variety and its serum concentration with repeated implantation failure (RIF). Setting and Design: The design of the study was a cross-sectional study. Materials and Methods: Four hundred infertile women with a history of RIF and 400 healthy women undergoing the first in vitro fertilisation-embryo transfer attempt with successful delivery (controls) were enrolled in the study. Genomic DNA was extracted from peripheral blood leucocytes and genotyped by Tetra-Primer Amplification Refractory Mutation System-Polymerase Chain Reaction. Serum FGF-1 concentration was evaluated with enzyme-linked immunosorbent assay. Statistical Analysis Used: The ANOVA test was used to analyse the difference between the means of the groups. Results: In RIF group, the genotype frequencies of the GG, GA and AA were 59%, 33.5% and 7.5%, respectively, whereas in controls were 72.5%, 24% and 3.5%, respectively. The G and A allele frequencies in the RIF group were 75.75% and 24.25%, while in controls were 84.5% and 15.5%, respectively (P < 0.0001). We have also shown that serum FGF-1 concentration in RIF and control groups was 17 ± 3.55 and 23.62 ± 4.91 pg/mL, respectively (P = 0.008). We have also shown that AA genotype is significantly associated with decreased serum FGF-1 concentration in RIF (AA, GA and GG serum levels were 9.55 ± 2.65, 14 ± 3.35 and 22.55 ± 7.26 pg/mL, and in controls were 12.22 ± 2.27, 18.44 ± 5.98 and 26.66 ± 8.29 pg/mL, respectively). Conclusion: The current study suggests that a significant association between FGF-1 (rs34011) promoter polymorphism and its serum concentration with RIF. The study also suggests that AA genotype is linked to lower FGF-1 serum levels and may play a risk factor for RIF.

Investigating the role of killer cell immunoglobulin-like receptors and human leukocyte antigen genetic variants in hepatitis C virus infection.

The genetic diversity of killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) genes influences the host's immune response to viral pathogens. This study aims to explore the impact of five single nucleotide polymorphisms (SNPs) in KIR3DL2 and HLA-A genes on hepatitis C virus (HCV) infection. A total of 2251 individuals were included in the case-control study. SNPs including KIR3DL2 rs11672983, rs3745902, rs1654644, and HLA-A rs3869062, rs12202296 were genotyped. By controlling various confounding factors using a modified logistic regression model, as well as incorporating stratified analysis, joint effects analysis, and multidimensional bioinformatics analysis, we analyzed the relationship between SNPs and HCV infection. The logistic regression analysis showed a correlation between KIR3DL2 rs11672983 AA, KIR3DL2 rs3745902 TT, and increased HCV susceptibility (p < 0.01). Stratified analysis indicated that KIR3DL2 rs1654644 and HLA-A rs3869062 also heightened HCV susceptibility in certain subgroups. A linear trend of rising HCV infection rates was observed when combining KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT (ptrend = 0.007). Bioinformatics analysis suggested these SNPs' regulatory potential and their role in altering messenger RNA secondary structure, implying their functional relevance in HCV susceptibility. Our findings indicate that KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT are significantly associated with increased susceptibility to HCV infection.

Interactive Association of XRCC1, XRCC2, XRCC3, and TP53 Gene Polymorphisms With Gastrointestinal Cancer Risk: Insights From a Hospital-Based Case-Control Study.

BACKGROUND AND AIM: Gastrointestinal (GI) cancer presents a significant worldwide health burden, influenced by a combination of genetic and environmental factors. This study endeavors to explore the combined effects of the XRCC1, XRCC2, XRCC3, and TP53 genes that contribute to the heightened risk of GI cancer, shedding light on their combined influence on cancer susceptibility. MATERIALS AND METHODS: A total of 200 histologically confirmed cases of GI cancer and an equal number of controls were selected to examine genetic polymorphisms within the XRCC1, XRCC2, XRCC3, and TP53 genes using the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Odds ratios (OR) with 95% confidence intervals (CI) were calculated to assess the association of these polymorphisms with GI cancer susceptibility, with statistical significance (p ≤ 0.05). RESULTS: Logistic regression analysis confirmed strong evidence of synergistic interactions among specific variant genotypes. Notably, combinations such as heterozygous Arg/Ser+Ser/Ser genotype of TP53 Arg249Ser polymorphism with Arg/Trp+Trp/Trp genotype of XRCC1 Arg194Trp polymorphism (OR=2.64; 95% CI: 1.35-5.18; p=0.004), Arg/Gln+Gln/Gln genotype of XRCC1 at codon 399 (OR=5.04; 95% CI: 2.81-9.05; p=0.0001), Arg/His and His/His genotypes of XRCC2 Arg188His (OR=2.16; 95% CI: 1.06-4.39; p<0.032), and Thr/Met+Met/Met genotype of XRCC3 Thr242Met (OR=3.48; 95% CI: 1.79-6.77; p=0.0002) showed significant associations with GI cancer risk in the study population. CONCLUSIONS: The findings indicate a notable association between the combined effect of heterozygous variant genotypes of TP53 and variant genotypes of XRCC1, XRCC2, and XRCC3 on GI cancer risk. However, further research with a larger sample size and broad single nucleotide polymorphism (SNP) spectra is necessary to understand the interaction between genetic variations and environmental factors influencing GI cancer susceptibility.

The roles of ACE I/D and ACTN3 R577X gene variants in heat acclimation.

Roles of genes in heat acclimation (HA, repeated exercise-heat exposures) had not been explored. ACE I/D and ACTN3 R577X genetic polymorphisms are closely associated with outstanding exercise performances. This study investigated whether the two polymorphisms influenced the response to HA. Fifty young Han nationality male subjects were selected and conducted HA for 2 weeks. Exercise indicators (5-km run, push-up and 100-m run) were tested and rest aural thermometry (RTau) was measured before and after HA. ACE gene was grouped by I homozygote and D carrier, and ACTN3 gene was grouped by R homozygote and X carrier. Results showed that there were no differences between groups in age, body mass index, exercise indicators and RTau before HA. After HA, RTau of ACE I homozygote was lower than that of D carrier [F (1, 48) = 9.12, p = 0.004, η = 0.40]. Compared with RTau before HA, that of I homozygote decreased after HA (Δ = -0.26 °C, 95 % CI -0.34-0.18, p < 0.001), while that of D carrier did not change. There was a ACE gene × HA interaction in RTau [F (1, 48) = 14.26, p < 0.001, η = 0.48]. No effect of ACTN3 gene on RTau was observed. For exercise indicators, there were no differences between groups after HA, and no gene × HA interactions were observed. There may be a strong interaction of ACE gene and HA in the change of rest core temperature. I homozygote may have an advantage on improving heat tolerance.

Changes in the tissue elements of the gastric mucosa interacting with different strains of Helicobacter pylori, taking into consideration the patient's genotype.

The present study aimed to investigate the peculiarities of adaptation of tissue elements of the gastric mucosa during interaction with Helicobacter pylori, as determined by genetic characteristics of the bacterium and the host. Venous blood and biopsy samples of the mucosa of the antrum and body of the stomach from young patients (18 to 25 years old) were examined. The condition of the gastric mucosa was assessed using stained histological preparations. Venous blood was collected from the patients to ascertain the polymorphisms of the IL-lß and IL-IRN genes. The most pronounced changes were observed in the parameters of reparative regeneration of epithelial differentiation during colonization of the gastric mucosa by H. pylori strains carrying the CagA(+) and BabA2(+) genes. These included an increase in proliferation and apoptosis rates and alterations in epithelial differentiation markers characterized by elevated production of Shh and MUC5AC, as well as a reduction in the production of the protective mucin MUC6 by isthmus gland cells. The presence of the vacAs1 and vacAs2 genes of H. pylori results in a high level of apoptosis in epithelial cells without accelerating proliferation. It was found that after eradication, patients with preserved cellular infiltrates in their gastric mucosa plates were carriers of mainly the IL-1ß*T/IL-1RN*2R haplotypes after 12 months.

Pon1 and Sult1a1 Polymorphisms and Breast Cancer Among Young Women in Brazil.

Purpose: To investigate the association of genetic polymorphisms Gln192Arg and Leu55Met of Paraoxonase 1 (PON1) gene, and Arg213His of Sulfotransferase 1A1 (SUT1A1) gene with occurrence of breast cancer among young women living in Rio de Janeiro city. Methods: This is a hospital-based case-control study including 265 women aged 18-35 years, diagnosed with breast cancer at National Cancer Institute; and 277 controls in the same age group selected among women patients and companions of three general hospitals from Rio de Janeiro public health network. Polymorphisms genotyping was performed using the PCR-RFLP technique. Results: For PON1 gene, breast cancer women had a greater chance of being homozygote for Leu55Met polymorphism (ORadjusted = 1.42, 95% CI= 0.67-3.00, recessive model) and a lower chance of having at least one allele of Gln192Arg polymorphism (ORadjusted = 0.75, 95% CI = 0.50-1.13, dominant model), but without statistical significance. Accordingly, frequency of the haplotype Met55/Arg192 was lower among breast cancer women, but no statistically significant association was observed (ORadjusted = 0.85; 95% CI = 0.48-1.51). SULT1A1 His/His genotype was significantly associated with a protective effect for breast cancer (OR adjusted = 0.51, 95% CI = 0.28-0.91, recessive model). Conclusion: Arg213His polymorphism of SUT1A1 gene showed a protective effect against breast cancer among Brazilian young women. More studies with different designs are needed to understand the role of PON1 and SULT1A1 polymorphisms in breast cancer development in young Brazilian women.

Genetic Variation and Stroke Recovery: The STRONG Study.

BACKGROUND: Genetic association studies can reveal biology and treatment targets but have received limited attention for stroke recovery. STRONG (Stroke, Stress, Rehabilitation, and Genetics) was a prospective, longitudinal (1-year), genetic study in adults with stroke at 28 US stroke centers. The primary aim was to examine the association that candidate genetic variants have with (1) motor/functional outcomes and (2) stress-related outcomes. METHODS: For motor/functional end points, 3 candidate gene variants (ApoE ε4, BDNF [brain-derived neurotrophic factor], and a dopamine polygenic score) were analyzed for associations with change in grip strength (3 months-baseline), function (3-month Stroke Impact Scale-Activities of Daily Living), mood (3-month Patient Health Questionnaire-8), and cognition (12-month telephone-Montreal Cognitive Assessment). For stress-related outcomes, 7 variants (serotonin transporter gene-linked promoter region, ACE [angiotensin-converting enzyme], oxytocin receptor, FKBP5 [FKBP prolyl isomerase 5], FAAH [fatty acid amide hydrolase], BDNF, and COMT [catechol-O-methyltransferase]) were assessed for associations with posttraumatic stress disorder ([PTSD]; PTSD Primary Care Scale) and depression (Patient Health Questionnaire-8) at 6 and 12 months; stress-related genes were examined as a function of poststroke stress level. Statistical models (linear, negative binomial, or Poisson regression) were based on response variable distribution; all included stroke severity, age, sex, and ancestry as covariates. Stroke subtype was explored secondarily. Data were Holm-Bonferroni corrected. A secondary replication analysis tested whether the rs1842681 polymorphism (identified in the GISCOME study [Genetics of Ischaemic Stroke Functional Outcome]) was related to 3-month modified Rankin Scale score in STRONG. RESULTS: The 763 enrollees were 63.1±14.9 (mean±SD) years of age, with a median initial National Institutes of Health Stroke Scale score of 4 (interquartile range, 2-9); outcome data were available in n=515 at 3 months, n=500 at 6 months, and n=489 at 12 months. At 1 year poststroke, the rs6265 (BDNF) variant was associated with poorer cognition (0.9-point lower telephone-Montreal Cognitive Assessment score, P=1×10-5). For stress-related outcomes, rs4291 (ACE) and rs324420 (FAAH) were risk factors linking increased poststroke stress with higher 1-year depression and PTSD symptoms (P<0.05), while rs4680 (COMT) linked poststroke stress with lower 1-year depression and PTSD. Findings were unchanged when considering stroke subtype. STRONG replicated GISCOME: rs1842681 was associated with lower 3-month modified Rankin Scale score (P=3.2×10-5). CONCLUSIONS: This study identified genetic associations with cognitive function, depression, and PTSD 1 year poststroke. Genetic susceptibility to PTSD and depressive symptoms varied according to the amount of poststroke stress, underscoring the critical role of lived experiences in recovery. Together, the results suggest that genetic association studies provide insights into the biology of stroke recovery in humans.

The role of tissue persistent organic pollutants and genetic polymorphisms in patients with benign and malignant kidney tumors.

This study aimed to explore whether there is an association between environmental exposure to POPs and kidney tumor induction, and whether blood POP concentrations reflect kidney tissue concentrations. POP derivatives were determined in blood, tumor tissue, tumor surrounding tissue, and perirenal fat tissue samples taken from patients who underwent surgery for renal tumors. A voluntary control group was recruited for blood and urine samples as well. Urinary excretions of o,o'-dityrosine, chlorotyrosine, nitrotyrosine, and 8-OHdG were measured in the same patients. The possible role of genetic polymorphisms in CYP1A1, GST isozymes P, M, and T, and hOGG1 genes on the predisposition to renal cancer was investigated. Some POPs have been found to be associated with kidney cancer, as evidenced by their significantly high ORs. 8-OHdG levels were significantly higher compared to the control group. The GSTT1 null polymorphism can be a risk factor for malignant but not for benign kidney tumors.

Universal Lineage-Independent Markers of Multidrug Resistance in Mycobacterium tuberculosis.

(1) Background: This study was aimed to identify universal genetic markers of multidrug resistance (MDR) in Mycobacterium tuberculosis (Mtb) and establish statistical associations among identified mutations to enhance understanding of MDR in Mtb and inform diagnostic and treatment development. (2) Methods: GWAS analysis and the statistical evaluation of identified polymorphic sites within protein-coding genes of Mtb were performed. Statistical associations between specific mutations and antibiotic resistance were established using attributable risk statistics. (3) Results: Sixty-four polymorphic sites were identified as universal markers of drug resistance, with forty-seven in PE/PPE regions and seventeen in functional genes. Mutations in genes such as cyp123, fadE36, gidB, and ethA showed significant associations with resistance to various antibiotics. Notably, mutations in cyp123 at codon position 279 were linked to resistance to ten antibiotics. The study highlighted the role of PE/PPE and PE_PGRS genes in Mtb's evolution towards a 'mutator phenotype'. The pathways of acquisition of mutations forming the epistatic landscape of MDR were discussed. (4) Conclusions: This research identifies marker mutations across the Mtb genome associated with MDR. The findings provide new insights into the molecular basis of MDR acquisition in Mtb, aiding in the development of more effective diagnostics and treatments targeting these mutations to combat MDR tuberculosis.

Genetic and epigenetic analyses of IFN-γ gene proximal promoter region underlying positive correlation between persistently high anti-SARS-CoV-2 IgG and IFN-γ among COVID-19 vaccinated Bangladeshi adults.

IFN-γ is an immunological modulator influencing IgG isotype and concentration, which present a correlate of protection to evaluate vaccine efficacy. As transiently expressed, stable genetic and epigenetic signatures of the cytokine's expression may exist. This study investigates correlation between plasma IFN-γ and anti-SARS-CoV-2 IgG levels, seeking genetic polymorphisms and epigenetic variations within the IFN-γ gene proximal promoter. 200 COVID-19-vaccinated adults were classified into seropositive and seronegative groups based on plasma anti-SARS-CoV-2 IgG. Upon correlation analysis between anti-SARS-CoV-2 IgG and IFN-γ levels, IFN-γ gene proximal promoter region was subjected to nucleotide sequencing for two subsets: seronegative (21 < Days post-vaccination ≤180, n = 11) and seropositive (IgG > Q3 and Days post-vaccination >180, n = 24). Relative unmethylation of IFN-γ proximal promoter was assessed for the latter subset and its correlation with plasma IFN-γ and IgG levels was evaluated. A statistically significant positive correlation (r = 0.492, p = 0.018) was observed between IFN-γ and anti-SARS-CoV-2 IgG in the seropositive group with persistently high IgG titre (IgG > Q3, Days elapsed post-vaccination >180). A heterozygous 5'-UTR variant (rs776667149:C>T) identified in one seronegative individual revealed a potential impact on PKR-mediated translational attenuation of IFN-γ mRNA. No significant correlation was found between IFN-γ proximal promoter unmethylation and its plasma levels among HAR individuals with Days post-vaccination of either >180 (r = 0.14, p = 0.679) or < 180 (r = -0.062, p = 0.693). This study demonstrates an extent of humoral immunity against SARS-CoV-2 among COVID-19 vaccinated Bangladeshi population. This study suggests plasma IFN-γ may play a role in maintaining persistent anti-SARS-CoV-2 IgG levels, which warrants further investigation along with genetic and/or epigenetic basis to fully establish its protective nature in COVID-19 vaccination.

Genetic Polymorphisms in Glutathione S-Transferase (GST) Gene and Their Correlation with Toxicity of Chemotherapy in Breast Cancer Patients.

BACKGROUND: Glutathione S-Transferase (GST) is a family of phase II metabolizing enzymes contribute to detoxification and elimination of variety of endogenous as well as exogenous xenobiotics including chemotherapeutic agents. The comprehensive knowledge on the impact of genetic polymorphisms in GST) enzyme coding gene will help to understand the clinical outcomes in breast cancer patients treated with either Adriamycin or paclitaxel or combination of both. In this study we attempted to assess the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and their association with Adriamycin and Paclitaxel induced toxicity reactions in breast cancer patients. METHODS: Two hundred BC patients receiving Adriamycin and Paclitaxel chemotherapy were enrolled in this study and chemotherapy induced hematological and non-hematological toxicity reactions were noted. The polymorphisms in GSTM1, GSTP1 and GSTT1 gene were studied by PCR and RFLP analysis. RESULTS: After the univariate analysis of the genetic polymorphisms of GSTM1, GSTP1 and GSTT1 showed that GSTT1 null genotype showed significant association with neutropenia (OR=2.84, 95% CI: 1.06-7.56; p=0.036) in breast cancer patients treated with Adriamycin and GSTT1 null genotype in patients with >1 CINV toxicity confirmed significant correlation (OR=3.75, 95% CI: 1.46-9.59; p=0.005). The genetic polymorphisms of GSTP1 (exon 5) A/G heterozygous genotype was significant in grade >1 toxicity reactions of mucositis (OR=3.22, 95% CI: 1.06-9.71; p=0.037) in breast cancer patients administered with Paclitaxel chemotherapy. CONCLUSION: The findings obtained from this study proposed significant involvement of GSTT1-null genotype in hematological neutropenia toxicity in response to Adriamycin and GSTM1-null genotype showed negative association with non-hematological toxicity (bodyache) in response to Paclitaxel.

Association of angiotensin converting enzyme gene insertion/deletion polymorphism with diabetic retinopathy in middle-aged Indians with type 2 diabetes mellitus.

OBJECTIVES: There are conflicting reports regarding the association of angiotensin 1 converting enzyme (ACE) gene polymorphism with diabetic retinopathy (DR). We compared ACE gene insertion/deletion (I/D) polymorphism between patients with and without DR in a middle-aged Indian population. The secondary outcome measure was the comparison of ACE gene I/D polymorphism in different grades of DR severity. METHODS: Institutional cross-sectional case-control study with middle-aged (45-64 years) type 2 diabetes patients from Eastern India with DR (DR group) and without DR (NODR group). Polymerase chain reaction (PCR) was used to determine the ACE gene I/D polymorphism through primers flanking the polymorphic region of 287 bp Alu repeat sequence in intron 16. RESULTS: Genotyping for the ACE gene I/D polymorphisms were done for 107 patients in each group. The presence of DR had no significant association with the prevalence of ACE I/D genotype compared to those without DR either in the recessive model (p=0.588) or in the dominant model (p=0.891). The allele contrast was also similar between DR and NODR (p=0.837) groups. The severity of retinopathy was associated with the ACE I/D genotype in the recessive model (p=0.043) but not in the dominant model (p=0.136). However, the severity of retinopathy was associated with allele contrast (p=0.016). CONCLUSIONS: The ACE gene polymorphism was not associated with diabetic retinopathy in middle-aged Indian patients with type 2 diabetes in our study. However, the severity of DR was associated with the ACE gene polymorphism in these patients.

Inflammatory Response Genes' Polymorphism Associated with Risk of Rheumatic Heart Disease.

Rheumatic heart disease (RHD) caused by group A streptococcus infection is one of the most important reasons of cardiovascular morbidity and mortality in low- and middle-income countries. Aberrant host immune response modulated by polymorphisms in inflammatory response genes plays an important role in RHD pathogenesis. This study aimed to determine risk-associated polymorphic variants in inflammatory response genes in Caucasian RHD patients. A total of 251 Caucasian RHD patients and 300 healthy donors were recruited for this study, and 27 polymorphic sites in 12 genes (TLR1, TLR2, TLR4, TLR6, IL1B, IL6R, IL6, IL10, IL12RB1, IL12B, TNF and CRP) were analyzed using allele-specific PCR. It was demonstrated that the polymorphic variants rs1800871 and rs1800872 in the IL10 gene, rs 1130864, rs3093077 and rs1205 in the CRP gene, rs375947 in the IL12RB1 gene, rs 5743551 and rs5743611 in the TLR1 gene, and rs3775073 in the TLR6 gene can modify RHD risk in a gender- and age-dependent manner. The obtained results can be used to determine the personalized risk of RHD in healthy donors during medical examination or screening, as well as to develop appropriate early prevention strategies targeting RHD in the risk groups.

Identification of an Allele-Specific Transcription Factor Binding Interaction that May Regulate PLA2G2A Gene Expression.

The secreted phospholipase A2 (sPLA2) isoform, sPLA2-IIA, has been implicated in a variety of diseases and conditions, including bacteremia, cardiovascular disease, COVID-19, sepsis, adult respiratory distress syndrome, and certain cancers. Given its significant role in these conditions, understanding the regulatory mechanisms impacting its levels is crucial. Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs), including rs11573156, that are associated with circulating levels of sPLA2-IIA. The work in the manuscript leveraged 4 publicly available datasets to investigate the mechanism by which rs11573156 influences sPLA2-IIA levels via bioinformatics and modeling analysis. Through genotype-tissue expression (GTEx), 234 expression quantitative trait loci (eQTLs) were identified for the gene that encodes for sPLA2-IIA, PLA2G2A. SNP2TFBS was used to ascertain the binding affinities between transcription factors (TFs) to both the reference and alternative alleles of identified eQTL SNPs. Subsequently, candidate TF-SNP interactions were cross-referenced with the ChIP-seq results in matched tissues from ENCODE. SP1-rs11573156 emerged as the significant TF-SNP pair in the liver. Further analysis revealed that the upregulation of PLA2G2A transcript levels through the rs11573156 variant was likely affected by tissue SP1 protein levels. Using an ordinary differential equation based on Michaelis-Menten kinetic assumptions, we modeled the dependence of PLA2G2A transcription on SP1 protein levels, incorporating the SNP influence. Collectively, our analysis strongly suggests that the difference in the binding dynamics of SP1 to different rs11573156 alleles may underlie the allele-specific PLA2G2A expression in different tissues, a mechanistic model that awaits future direct experimental validation. This mechanism likely contributes to the variation in circulating sPLA2-IIA protein levels in the human population, with implications for a wide range of human diseases.

The Frequencies distribution of CYP3A5 rs776746 and ABCB1 rs1045642 polymorphisms in the west Algerian population and relationships with pharmacogenetics.

Introduction: Pharmacogenetic markers, such as the ATP Binding Cassette (ABCB1) and cytochrome P450 (CYP) 3A5 enzymes, play a crucial role in personalized medicine by influencing drug efficacy and toxicity based on individuals' or populations' genetic variations.This study aims to investigate the genetic polymorphisms of CYP3A5 (rs776746) and ABCB1 (rs1045642) in the West Algerian population and compare the genotypes and allelic distributions with those of various ethnic groups. Methods: The study involved 472 unrelated healthy subjects from the Western Algerian population. DNA genotyping was performed using TaqMan allelic discrimination assay. The variants in our population were compared to those in other ethnic groups available in the 1000 Genomes Project. Genotype and allele frequencies were calculated using the chi-square test and the Hardy-Weinberg equilibrium (HWE). Results: The minor allele frequencies were found to be 0.21 for CYP3A5 6986A and 0.34 for ABCB1 3435T. These frequencies were similar to those observed in North African populations, while notable differences were observed in comparison to certain Caucasian and African populations. Conclusion: The difference in the allelic and genotypic distribution of these polymorphisms emphasize the need for dose adjustments in drugs metabolized by CYP3A5 and transported by ABCB1 to optimize treatments outcomes.

Increased prevalence of the null allele of the p.Arg577Ter variant in the ACTN3 gene in Brazilian long-distance athletes: A retrospective study.

INTRODUCTION: The phenotypic consequences of the p.Arg577Ter variant in the α-actinin-3 (ACTN3) gene are suggestive of a trade-off between performance traits for speed and endurance sports. Although there is a consistent association of the c.1729C allele (aka R allele) with strength/power traits, there is still a debate on whether the null allele (c.1729T allele; aka X allele) influences endurance performance. The present study aimed to test the association of the ACTN3 p.Arg577Ter variant with long-distance endurance athlete status, using previously published data with the Brazilian population. METHODS: Genotypic data from 203 long-distance athletes and 1724 controls were analysed in a case-control approach. RESULTS: The frequency of the X allele was significantly higher in long-distance athletes than in the control group (51.5% vs. 41.4%; p = 0.000095). The R/X and X/X genotypes were overrepresented in the athlete group. Individuals with the R/X genotype instead of the R/R genotype had a 1.6 increase in the odds of being a long-distance athlete (p = 0.012), whereas individuals with the X/X genotype instead of the R/R genotype had a 2.2 increase in the odds of being a long-distance athlete (p = 0.00017). CONCLUSION: The X allele, mainly the X/X genotype, was associated with long-distance athlete status in Brazilians.

Genetic polymorphisms associated with developmental defects of enamel: A systematic review.

BACKGROUND: Polymorphisms in genes related to enamel formation and mineralization may increase the risk of developmental defects of enamel (DDE). AIM: To evaluate the existing literature on genetic polymorphisms associated with DDE. DESIGN: This systematic review was registered in the PROSPERO (CRD42018115270). The literature search was performed in PubMed, Scopus, Web of Science, LILACS, BBO, Cochrane Library, and in the gray literature. Observational studies assessing the association between DDE and genetic polymorphism were included. The Newcastle-Ottawa Scale was used to assess the risk of bias. RESULTS: One thousand one hundred and forty-six articles were identified, and 28 met the inclusion criteria. Five studies presented a low risk of bias. Ninety-two genes related to enamel development, craniofacial patterning morphogenesis, immune response, and hormone transcription/reception were included. Molar-incisor hypomineralization (MIH) and/or hypomineralization of primary second molars (HPSM) were associated with 80 polymorphisms of genes responsible for enamel development, immune response, morphogenesis, and xenobiotic detoxication. A significant association was found between the different clinical manifestations of dental fluorosis (DF) with nine polymorphisms of genes responsible for enamel development, craniofacial development, hormonal transcription/reception, and oxidative stress. Hypoplasia was associated with polymorphisms located in intronic regions. CONCLUSION: MIH, HPSM, DF, and hypoplasia reported as having a complex etiology are significantly associated with genetic polymorphisms of several genes.

Analysis of human papillomavirus type 16 E4, E5 and L2 gene variations among women with cervical infection in Xinjiang, China.

BACKGROUND: There is a high incidence of cervical cancer in Xinjiang. Genetic variation in human papillomavirus may increase its ability to invade, spread, and escape host immune response. METHODS: HPV16 genome was sequenced for 90 positive samples of HPV16 infection. Sequences of the E4, E5 and L2 genes were analysed to reveal sequence variation of HPV16 in Xinjiang and the distribution of variation among the positive samples of HPV16 infection. RESULTS: Eighty-one of the 90 samples of HPV16 infection showed variation in HPV16 E4 gene with 18 nucleotide variation sites, of which 8 sites were synonymous variations and 11 missense variations. 90 samples of HPV16 infection showed variation in HPV16 E5 and L2 genes with 16 nucleotide variation sites (6 synonymous, 11 missense variations) in the E5 gene and 100 nucleotide variation sites in L2 gene (37 synonymous, 67 missense variations). The frequency of HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A was higher in the case groups than in the control groups. CONCLUSIONS: Phylogenetic tree analysis showed that 87 samples were European strains, 3 cases were Asian strains, there were no other variations, and G4181A was related to Asian strains. HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A were significantly more frequent in the case groups than in the control groups.

Genetic diversity of the PvMSP-3α gene in Plasmodium vivax isolates circulating in the National Capital Region (NCR) of India.

Malaria is still a public health problem in tropical countries like India; major malaria parasite species are Plasmodium falciparum and P. vivax. Of which, P. vivax is responsible for ∼40% of the malaria burden at least in the Indian scenario. Unfortunately, there is limited data on the population structure and genetic diversity of P. vivax parasites in India. In this study, we investigated the genetic diversity of P. vivax strains in the South-west district, Delhi and, Nuh district, Haryana [National Capital Region (NCR)], using a polymorphic marker- P. vivax merozoite surface protein-3α (PvMSP-3α) gene. Dried blood spots from microscopically confirmed P. vivax patients were used for investigation of the PvMSP-3α gene. PCR-RFLP was performed on the PvMSP-3α gene to investigate the genotypes and allelic variability with HhaI and AluI restriction enzymes. In total, 40 successfully PCR amplified PvMSP-3α gene segments were subjected to RFLP analysis. Amplified products showed three different base pair size variations viz. genotype A in 31(77.5%), genotype B in 4(10%) and genotype C in 5(12.5%) P. vivax specimens. RFLP with HhaI and AluI revealed 17 (H1-H17) and 25 (A1-A25) allelic variants, respectively. Interestingly, two similar sub-allelic variants, ie. H8 (with HhaI), and A4 (with AluI) clustered within the rural area of Nuh district, Haryana in two samples. With this study, we propose to commission such type of genetic diversity analysis of P. vivax to investigate the circulating genotypes of the parasites from distinct geographical locations across India, that can have significant implications in understanding the population structures of P. vivax.

Genetic polymorphisms and their association with neurobiological and psychological factors in anorexia nervosa: a systematic review.

Background and aims: Anorexia nervosa (AN) is a complex neuropsychiatric disorder. This systematic review synthesizes evidence from diverse studies to assess and investigate the association between gene polymorphisms and psychological and neurobiological factors in patients with AN. Methods: A systematic search across PubMed, PsycINFO, Scopus, and Web of Science databases, along with manual searching, was conducted. The review protocol was approved by PROSPERO (CRD42023452548). Out of 1,250 articles, 11 met the inclusion criteria. The quality of eligible articles was assessed using the Newcastle-Ottawa Scale (NOS) tool. The systematic review followed the PRISMA guidelines. Results: The serotoninergic system, particularly the 5-HTTLPR polymorphism, is consistently linked to altered connectivity in the ventral attention network, impaired inhibitory control, and increased susceptibility to AN. The 5-HTTLPR polymorphism affects reward processing, motivation, reasoning, working memory, inhibition, and outcome prediction in patients with AN. The dopaminergic system, involving genes like COMT, DRD2, DRD3, and DAT1, regulates reward, motivation, and decision-making. Genetic variations in these dopaminergic genes are associated with psychological manifestations and clinical severity in patients with AN. Across populations, the Val66Met polymorphism in the BDNF gene influences personality traits, eating behaviors, and emotional responses. Genes like OXTR, TFAP2B, and KCTD15 are linked to social cognition, emotional processing, body image concerns, and personality dimensions in patients with AN. Conclusion: There was an association linking multiple genes to the susceptibly and/or severity of AN. This genetic factor contributes to the complexity of AN and leads to higher diversity of its clinical presentation. Therefore, conducting more extensive research to elucidate the underlying mechanisms of anorexia nervosa pathology is imperative for advancing our understanding and potentially developing targeted therapeutic interventions for the disorder.Systematic review registration: [https://clinicaltrials.gov/], identifier [CRD42023452548].