Background Tumor Necrosis Factor Alpha (TNF-α), is a proinflammatory cytokine in the pathogenesis of Polycystic Ovary Syndrome (PCOS). In order to investigate the role of rs1800629 and rs1799964 polymorphisms in relation to anthropometric measures, family history of complex diseases, diet and clinical features, we performed a case control study in PCOS women from South India. Methods A total of 589 samples comprising of 283 patients and 306 controls were enrolled in the present study. Patients were selected based on Rotterdam criteria and ultrasound scanned normal women were selected as controls. Following extraction of DNA, genotyping for rs1800629 and rs1799964 was performed by polymerase chain reaction using tetra primers and PCR-RFLP respectively. Results The distribution of genotypes for rs1799964 was significantly different between the groups (p =0.001), however it was not for rs1800629. Haplotype analysis revealed a significant difference between patients and controls. The predisposing and protective role of haplotype with mutant allele at both loci (combination 3) and haplotype with mutant allele at either loci was reflected by the over representation of combination 3 in patients and combination 2 in controls respectively. In addition, rs1799964 showed an association with dietary habit, clinical hyperandrogenism and AAO. The modifying role of TT genotype on age at onset was noted in quartile analysis. ConclusionReplicative studies on the influence of TNF-α polymorphism in different ethnic groups may identify the potentiality of these polymorphisms as markers of inflammation and in turn may help the clinicians for the better management of the condition.

Background The increased complications to the mother and fetus during or after pregnancy and birth are often caused by a wide array of pathogenic organisms mostly belonging to the TORCH group [toxoplasmosis, rubella, cytomegalovirus (CMV), and herpes simplex virus (HSV)]. These agents cause asymptomatic or mild infection in the mother while serious consequences in fetus. The present study was aimed to find significant etiological pathogens in the causation of high risk pregnancy (HRP) in South Indian population. Material and Methods A total of 1, 158 HRP women (2010158 HRP women ( -2013 from Modern Government Maternity Hospital, Hyderabad were considered. Two milliliter of blood was obtained and the serum was analyzed for IgG and IgM antibodies against TORCH agents by ELISA. Results Twenty-five percent of the study group had fetal congenital malformation in the present pregnancy (Group 1; N = 291) while 75 % showed bad obstetric history (BOH) (Group 2; N = 867). Maternal age of B25 years, primi gravida, and consanguinity showed predisposing role for Group 1 while maternal age C30 years and C 3 gravida were contributing risk for Group 2. The seropositvity in 123HRP women for toxoplasma, rubella, CMV, and HSV was 28, 84, 92, and 61 %, respectively for IgG while it was 6, 3, 4, and 3 % for IgG ? IgM. Total seropositvity of toxoplasma, rubella, CMV, and HSV in Group 1 was 29, 97, 97, and 62 % while it was 36, 84, 97, and 65 % in Group 2, respectively. Conclusion Maternal age of B25 years, primi gravida, and consanguinity contributed to fetal congenital malformation in the present pregnancy while maternal age of C30 years and C 3 gravida towards BOH. Toxoplasma is protective while rubella and CMV are the infectious agents for HRP. Among the groups, toxoplasma and rubella conferred a predisposing risk towards Group 2 and Group 1, respectively. Sixty-one percent seropositvity of HSV in relation to bad obstetric outcome is the highest prevalence reported so far in India.

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Background Polycystic ovary syndrome (PCOS) is a condition with central feature of hyperandrogensism that affects 5-12 % of women worldwide. P450sec the cholesterol side chain cleavage enzyme encoded by CYP11A1 gene is instrumental in the synthesis of sex hormones. A promoter pentanucleotide repeat (tttta) n polymorphism of this gene is reported to be associated with several hormone related diseases including PCOS. Here we aimed to examine the involvement of CYP11A1 polymorphism with PCOS susceptibility in a case-control study conducted among South Indian women. Methods A total of 542 subjects comprised of 267 PCOS patients and 275 controls were recruited. DNA was extracted from blood and CYP11A1 (tttta) n polymorphism was genotyped by PCR-PAGE. Results Fifteen different alleles ranging between 2-16 repeats were identified in the studied group and the most frequent allele observed in controls was of 8 repeats. The presence of >8 repeat allele was common in patients (64 % vs. 38 %) and showed a three-fold risk for PCOS susceptibility than controls (OR=2.93; p<0.05). PCOS women with higher BMI were markedly elevated in early quartile (p<0.05). Conclusion CYP11A1 (tttta) n repeat polymorphism appeared to be a potential molecular marker for PCOS risk in our population. Gene-gene and gene-environmental interactions with respect to obesity may play a role in the early onset of this multifactorial condition. This is the first report from South India; however, replicative studies considering other probable causative factors for PCOS risk are warranted.

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Background Polycystic ovary syndrome (PCOS) is an endocrine disorder exhibiting variable age at onset of clinical features allied with complex diseases in the later life. ACE is a pleiotropic molecule associated with various pathophysiological functions. The present study was aimed to establish the frequency of ACE I/D gene polymorphism in patients and controls and to assess the influence of this polymorphism on anthropometric and various clinical features of the condition. Methods ACE I/D genotyping was carried out in 259 PCOS patients and 315 healthy ultrasound scanned women of South Indian origin.Results The distribution of DD, ID and II genotypes in patients was 39, 37 and 24 %, whereas in the controls it was 31, 51 and 18 % respectively. Significant difference was observed in the genotypic frequency distributions between the patients and controls, however the allelic frequencies did not vary between the groups (p>0.05). Quartile analysis revealed preponderance of DD genotype in the first two quartiles and a linear increase of II genotype from first to the last quartiles. Further, Multiple Logistic regression analysis revealed significant association of ACE I/D gene polymorphism with acanthosis and age at onset (AAO) of the syndrome (p<0.05). Conclusion The present study is the first report to highlight the predisposing role of DD and protective role of ID genotype towards PCOS. Patients with single or double dose of D allele may develop PCOS symptoms at an early age and also significantly associated with acanthosis, a marker of insulin resistance.

Polycystic Ovary Syndrome (PCOS) is a multifactorial reproductive healthcare problem affecting 4-12% of women and a leading cause of female infertility worldwide. The potential genetic contributors of PCOS are unclear. However, over the past decade emerging evidence has shown that increased Oxidative Stress (OS) and decreased antioxidant status were often linked with PCOS. The present case-control study was aimed to assess the reactive oxygen species induced OS in women from South India. A total of 164 individuals comprising of 89 patients and 75 controls were enrolled in the present study. For all the subjects, the frequency of micronucleated cells (MNC) in epithelial samples and serum Malondialdehyde (MDA) levels were estimated to assess genomic instability and cytotoxicity respectively. A statistically significant difference between the groups were identified with respect to Body Mass Index, Waist to Hip Ratio, luteinizing hormone and prolactin levels (< 0.05), however the mean follicle stimulating hormone was not different between the groups (p = 0.055). The frequency of MN cells (5.89 ± 4.86 vs. 2.24 ± 2.01) and mean serum MDA (360.84 ± 87.08 vs. 301.70 ± 82.82) levels were considerably higher in patients than controls (p = < 0.0001), furthermore, a positive correlation was observed between MNC and MDA levels in patients (r = 0.349, p = 0.0008) and not in controls (r = 0.104, p = 0.37), suggest high OS in PCOS women. Therefore, MN assay and serum MDA levels may serve together or individually as biomarkers of OS in PCOS women.

ABBREVIATIONS MTHFD1Methylenetetrahydrofolate dehydrogenase NTD Neural tube defect POE Parent-of-origin effects TDT Transmission disequilibrium test AIM This study aimed to evaluate the role of methylenetetrahydrofolate dehydrogenase (MTHFD1) G1958A variant (rs2236225) as a 'maternal, paternal, or embryonic' genetic risk factor for neural tube defect (NTD) susceptibility. It also estimated differential associations based on type of NTD, offspring sex, maternal-paternal-offspring genotype incompatibility, and parent-of-origin effects (POE) using both case-control and family-based approach. In addition, genotype impact on serum folate levels was also assessed.METHOD The study population (n=900) consisted of 120 NTD case-parent triads (n=12093=360) and 180 healthy control-parent triads (n=18093=540) from South India. Umbilical cord tissues were collected from those with NTD and control newborn infants, and blood samples from case and control parents. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis used were SPSS, transmission disequilibrium test and POE. Serum folate levels were estimated using enzyme-linked immunosorbent assay. RESULTSIn the case-control study, those with the MTHFD1 G1958A variant were associated with around twofold risk of anencephaly (p=0.01) and spina bifida (p<0.01). Among parents, fathers were associated with around twofold risk of having an offspring with anencephaly (p<0.01). Considering offspring sex, the A allele in single or double dose conferred around two-to fourfold risk of anencephaly (p=0.01), spina bifida (p<0.01), and encephalocele (p<0.05) in females only. Maternal AA genotype was not associated independently but conferred threefold risk when combined with paternal GA genotype (p=0.01). Transmission disequilibrium and POE were not observed in controls (p>0.05) but revealed excess total (odds ratio [OR]=2.21; p<0.01) and paternal transmission (OR=7.00; p<0.01) of the G1958A allele to those with spina bifida, which remained the same for female cases (total transmission OR=3.00, p=0.01; paternal transmission OR=12.00, p<0.01). Increased serum folate levels were observed in case fathers with GA and AA genotypes than control fathers (p<0.01).INTERPRETATION Our research provides the first evidence supporting a paternal, rather than a maternal, transmission bias of MTHFD1 G1958A variant for NTD susceptibility in the offspring.Neural tube defects (NTDs) are a group of severe congenital malformations that develop when the neural tube fails to close properly during early embryogenesis. They include a range of malformations (e.g. anencephaly, spina bifida, and encephalocele), which further complicates the identification of risk factors. 1 Despite the successful establishment of folic acid supplementation and recent advances in genetics, epidemiology, and surgery, NTDs still represent the second most serious human birth defects after congenital heart defects.