Dopamine Receptor D2 gene Polymorphisms rs2005313, rs4274224, and rs4938019 in Pakistani Patients with Schizophrenia:a Diagnostic Tool for Schizophrenia

Haplotype-based association of HTR2A rs6311-rs6313 with early risperidone-clozapine response in Batak patients with schizophrenia.

BACKGROUND Risperidone-clozapine response varies substantially in schizophrenia. HTR2A polymorphisms may influence antipsychotic response, but rs6311-rs6313 haplotypes remain unexplored in the Indonesian Batak population. This study evaluated associations of HTR2A rs6311-rs6313 with early risperidone-clozapine response. METHODS This prospective observational case-control study included 160 Batak inpatients with schizophrenia, comprising 80 responders and 80 nonresponders to risperidone-clozapine therapy. Genetic analyses included Hardy-Weinberg equilibrium (HWE), minor allele frequency (MAF), linkage disequilibrium, genotype and allele association, haplotype, permutation testing, genetic models, and multivariable logistic regression. RESULTS Genotype distributions conformed to HWE (P > 0.05), with both variants showing a MAF of 0.28 and strong linkage disequilibrium (r2 = 0.969, D' = 0.98). The rs6311 GG/rs6313 CC genotype was significantly associated with nonresponse to risperidone-clozapine therapy [odds ratio (OR) = 3.69, 95% confidence interval (CI): 1.10-12.36; P = 0.034], while the rs6311 G/rs6313 C allele was also associated with nonresponse (OR = 1.71, 95% CI: 1.04-2.80; P = 0.034). The recessive model remained significant after multivariable adjustment (adjusted OR = 3.36, 95% CI: 1.02-11.07; P = 0.046). TA and CG haplotypes remained significant after 10 000 permutations (P = 0.0415 and P = 0.0416), whereas single-marker associations lost significance (P = 0.0607). CONCLUSION HTR2A variation was associated with early risperidone-clozapine response, with consistent signals under the recessive model and at the haplotype level. Haplotype associations remained significant after permutation correction, suggesting that haplotype analysis may provide a more robust approach for detecting pharmacogenetic contributions to treatment response.

Association of rs10741657 polymorphism in CYP2R1 gene with apparently healthy vitamin-D deficient Pakistani subjects

Objectives: To determine the association of polymorphism rs10741657 in the CYP2R1 gene with vitamin D deficiency in apparently healthy subjects. Method: The prospective, case-control study was conducted from June 2023 to January 2024 at the CREAM Lab of Army Medical College, Rawalpindi, and comprised vitamin D-deficient cases in group A and healthy controls in group B.  Genotyping of rs10741657 polymorphism in the CYP2R1 gene was performed using allele-specific polymerase chain reaction (AS-PCR). Genotypic and allelic frequencies, Hardy–Weinberg equilibrium, and genetic inheritance models were analysed using SNPStats, a web-based statistical software for genetic association studies. Results: Of the 300 subjects with a mean age of 43.56 ± 15.26 years, 150 (50%) were in group A, comprising 91 (61%) females and 59 (39%) males, with a mean age of 44.49 ± 15.12 years. There were 150 (50%) controls in group B, including 83 (55%) males and 67 (45%) females, with a mean age of 42.63 ± 15.40 years. The genotypic frequencies in group A were A/A 45(30%), A/C 101(67.34%), C/C 4(2.66%). The corresponding values in group B were 39(26%), 110(73.34%) and 1(0.66%). The allele frequency of A was 191 (64%) in vitamin D-deficient cases and 188 (63%) in healthy controls (p = 0.8775), while the C allele frequency was 109 (36%) in cases and 112 (37%) in controls (p = 0.8401). The genotype frequencies in cases were A/A 45 (30%), A/C 101 (67%), and C/C 4 (2.67%), compared to A/A 39 (26%), A/C 110 (73%), and C/C 1 (0.67%) in controls, with no statistically significant difference observed between the groups (p > 0.05). The inheritance genetic models suggested no association with vitamin D deficiency (p>0.05); codominant model – A/C odds ratio 0.70 (95% confidence interval: 0.45-1.23), C/C odds ratio 4.00 (95% confidence interval: 0.45-36.96); dominant model odds ratio 0.80 (95% confidence interval: 0.49-1.35); recessive model odds ratio 4.00 (95% confidence interval: 0.45-36.96); and overdominant model odds ratio 0.70 (95% confidence interval: 0.45-1.23). Conclusion: The A allele was found to be the most common variant of rs10741657 in both the groups. The rs10741657 polymorphism was not a risk for the susceptibility to vitamin D deficiency. No correlation of genotype with serum vitamin D levels was noted. Key Words: Allele-specific polymerase chain reaction, Single nucleotide polymorphism, Calcitriol, 25 Hydroxylase, Vitamin D binding protein.

Association of TGFA gene polymorphisms (rs11466297 and rs3732248) with polycystic ovary syndrome (PCOS): a case-control study.

OBJECTIVES Polycystic ovary syndrome (PCOS) is a complicated endocrine condition that causes ovarian dysfunction, metabolic problems, and hormonal irregularities. Genetic factors profoundly affect its pathogenesis. This study investigates the association between polymorphisms in the Transforming Growth Factor Alpha (TGFA) gene, specifically rs11466297 and rs3732248, and the risk of PCOS. METHODS We conducted a case-control study involving 200 individuals confirmed to have PCOS and 200 control subjects. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Amplification Refractory Mutation System (ARMS-PCR) procedures to genotype the TGFA SNPs rs11466297 A/C and rs3732248 G/A. We performed statistical analyses, including odds ratios (OR) and 95% confidence intervals (CI), to evaluate the relationship between the polymorphisms and the risk of PCOS. RESULTS Genotypic analysis revealed that the TGFA rs3732248 GA heterozygote was significantly associated with increased PCOS risk under the codominant model (OR = 2.16, 95% CI: 1.39-3.32, p < 0.001), dominant model (OR = 1.77, 95% CI: 1.18-2.65, p = 0.013), and overdominant model (OR = 2.26, 95% CI: 1.47-3.45, p = 0.001). All associations remained significant after Bonferroni correction (p < 0.025). For rs11466297, no significant association survived correction. PCOS patients had significantly higher BMI, waist circumference, total cholesterol, and triglycerides compared to controls (p < 0.001 for all). Haplotype analysis revealed no significant association between TGFA haplotypes and PCOS risk. CONCLUSION This study is the first to demonstrate that the TGFA rs3732248 polymorphism is significantly associated with PCOS susceptibility in an Iranian population. These findings provide novel genetic evidence supporting a role for TGFA in PCOS pathogenesis and warrant replication in larger independent cohorts.

Association of dopamine transporter gene DAT1 40-bp 3′ UTR VNTR polymorphism (rs28363170) with Psychiatric disorders susceptibility: A study from the Pakistani population

DOES RS11191580 NT5C2 AND DRD2-141C INS/DEL POLYMOPRHIMSM AFFECT SCHIZOPHRENIA SYMPTOMS SEVERITY IN BATAK POPULATION

Introduction Schizophrenia is a highly heritable psychiatric disorder with a complex genetic architecture. Variants in NT5C2 and DRD2 have been implicated in schizophrenia susceptibility; however, their relationships with symptom severity and cognitive impairment remain inconsistent across different ethnic populations. This study investigated the association of NT5C2 rs11191580 and DRD2 − 141C Ins/Del polymorphisms with schizophrenia, psychopathology, and cognitive function in the Batak population of North Sumatra, Indonesia. Methods A hospital-based case–control study was conducted involving 50 Batak patients with schizophrenia and 50 ethnically matched healthy controls. Genotyping of NT5C2 rs11191580 and DRD2 − 141C Ins/Del polymorphisms was performed using polymerase chain reaction. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Results Significant differences in genotype distributions were observed between schizophrenia patients and healthy controls for NT5C2 rs11191580 (p = 0.022) and DRD2 − 141C Ins/Del (p < 0.001). Neither polymorphism was associated with PANSS severity categories or PANSS total and subscale scores (all p > 0.05). Discussion Both NT5C2 rs11191580 and DRD2 − 141C Ins/Del polymorphisms were associated with schizophrenia susceptibility in the Batak population but not with symptom severity.

Lack of Association Between MIR155 Gene Variant rs767649 and Risk for Parkinson’s Disease

An important role of neuroinflammation in the pathogenesis of Parkinson’s disease (PD) has been proposed. Since some microRNAs (miRNAs), and miR-155 in particular, are involved in neuroinflammatory processes, a previous study reported an association between one of the most common single nucleotide variants (SNVs), rs767649, in the MIR155 gene, and risk for PD. The aim of the current study was to replicate this finding in a larger Spanish population case–control series. We analyzed genotype and allele frequencies of the MIR155 rs767649 SNV in a Spanish Caucasian cohort consisting of 459 PD patients and 460 age- and sex-matched healthy controls, using a TaqMan allelic discrimination assay specifically designed for rs767649. The genotype frequencies of the MIR155 rs767649, under codominant, dominant, recessive, and overdominant inheritance models, as well as allelic frequencies, showed no significant differences between PD patients and healthy controls. Likewise, the age at PD onset did not differ among the three MIR-155 rs767649 genotypes. These data did not identify a statistically significant association between MIR155 rs767649 variants and PD risk. However, the low frequency of the variant allele resulted in limited statistical power, and modest genetic effects cannot be excluded.