Significance of LHCGR polymorphisms in polycystic ovary syndrome: an association study.

This study was conducted to analyze the association of Luteinizing Hormone/Choriogonadotropin Receptor (LHCGR) gene rs4953616 and rs7371084 polymorphisms with the risk of polycystic ovary syndrome (PCOS) in Punjab, India. A total of 823 women (443 PCOS cases and 380 healthy controls) were enrolled in the present study. The polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP) was used for genotyping. Anthropometric parameters, lipid and hormonal profiles, were compared between the two groups. Demographic features were compared using Mann Whitney U test while the Chi-square test and odds ratios (ORs) were used to assess the genetic association and risk towards PCOS, respectively. A one-way analysis of variance (ANOVA) test was employed to analyze the correlation of genotypes with baseline parameters in PCOS cases. A statistically significant difference was revealed in the genotypic and allelic frequencies of rs4953616 polymorphism between PCOS cases and controls (p = 0.01 and p = 0.004, respectively). The mutant genotype (TT), mutant allele (T), and recessive model of rs4953616 polymorphism conferred 1.77, 1.3, and 1.5 times risk towards PCOS, respectively. No significant distribution for genotypes and alleles was found for rs7371084 in both groups (p = 0.25 and p = 0.26, respectively). In addition to dyslipidemia, PCOS women also had significantly higher body mass index (BMI) and waist-to-hip ratio (WHR), testosterone (T), and luteinizing hormone (LH). Upon haplotype analysis, the TT haplotype was found to be significantly associated with the increased risk of PCOS. Our results demonstrated a significant role of LHCGR rs4953616 polymorphism in the development of PCOS.

Role of tumor necrosis factor-alpha -238 G>A promoter region polymorphism on recurrent miscarriage: An association study and meta-analysis.

BACKGROUND: Recurrent miscarriage (RM) is defined as the loss of two or more consecutive pregnancies. A functional SNP, -238G>A in the promoter region of TNF-α, affects the gene transcription activity with implications on human pregnancy. Previous limited studies, linking the TNF-α -238 G>A to the risk of recurrent miscarriage have been inconclusive. MATERIAL AND METHOD: The PCR-RLFP technique was used to evaluate this polymorphism in 199 RM cases and 215 control women from Amritsar, Punjab. For a meta-analysis, a total of 13 eligible studies (including the present study) comprising 2947 cases and 2933 controls were included. To evaluate the association among different genetic models, odds ratio with a 95% confidence interval (CI) and chi-square were used. RESULTS: Genotype and allelic frequency did not differ significantly between both groups (p = .07 and p = .24, respectively). In the present meta-analysis, a significant association was found with the recessive model (OR-1.78 CI:1.24-2.55, p = .002). CONCLUSION: Although, TNF-α -238 G>A polymorphism did not provide any risk in the case-control study but provided risk towards the development of RM with the recessive genetic model in the pooled analysis.

Impact of Interleukin-10 Promoter Region Polymorphisms on Recurrent Miscarriage: A Case-Control Approach.

Background: Recurrent miscarriage (RM), defined as two or more consecutive miscarriages prior to the 20th week of gestation is characterised by multifactorial aetiology. The prevalence of RM varies from 0.8% to 13.5% amongst women of reproductive age. The aetiological basis of RM has been traced to chromosomal, anatomic, hormonal and immunologic factors while half of the cases remain idiopathic. Aims: This study aimed to investigate the association of interleukin-10 (IL-10) polymorphisms with RM amongst the Indian population. Settings and Design: The present study included a total of 414 individuals including RM women (n = 199) with two or more pregnancy losses and healthy women (n = 215) without any previous history of pregnancy loss were taken as the control group. Materials and Methods: Demographic features and reproductive history of women with RM and healthy women were taken. Genotype analysis of IL-10 polymorphisms rs1800872 and rs1800896 was performed using the polymerase chain reaction (PCR) restriction fragment length polymorphism and amplification mutation refractory system PCR, respectively. Statistical Analysis Used: Student's t-test was used to compare the demographic features and reproductive history amongst both groups. Pearson's Chi-square was used to calculate the Hardy-Weinberg equilibrium, allelic and genotypic frequencies. All the statistical analyses were performed using the SPSS (version 21, IBM SPSS, NY, USA). Results: Our results suggested that the genotypic and allelic frequency of rs1800872 polymorphism did not differ significantly between RM cases and control women (P = 0.07 and P = 0.23, respectively). The GG genotype (P = 0.007) and G allele (P = 0.003) of rs1800896 were significantly associated with an increased risk of RM. A statistically significant difference was also found for the distribution of genetic models (dominant and co-dominant model) between both groups for rs1800896. However, haplotype analysis revealed that none of the haplotypes provides a risk for the progression of RM. Conclusion: The study is the first of its kind from our region and provides baseline data on the genetics of RM.

Analyzing the Impact of FSHR Variants on Polycystic Ovary Syndrome-a Case-Control Study in Punjab.

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic syndrome that involves hyperandrogenism, menstrual irregularities, and/or small cysts in one or both ovaries which might lead to infertility in women. The genetics of PCOS is heterogenous with the involvement of several genes reported in the hypothalamic-pituitary-gonadal axis. Follicular growth and steroidogenesis regulation are both critically dependent on follicle-stimulating hormone (FSH). The variants of FSHR cause abnormal folliculogenesis, steroidogenesis, and oocyte maturation at various stages of growth and may render women more susceptible to PCOS development. The present case-control study evaluated the association of FSHR rs6165 and rs6166 variants with PCOS. A total of 743 females were recruited. PCR-RFLP method was used for the genotypic analysis of FSHR polymorphisms. Obesity was examined according to the categorization of body mass index (BMI) and waist-hip ratio (WHR). Biochemical analysis, including a lipid profile, LH, FSH, and testosterone levels, was done in both PCOS women and controls. BMI and WHR revealed a statistically significant difference between PCOS cases and controls. Overall, levels of HDL were significantly lower, whereas cholesterol, triglycerides, LDL, and VLDL levels were higher in PCOS women (p < 0.05). The genotypic and allelic frequencies of rs6165 and rs6166 did not demonstrate significant differences when PCOS women were compared with the control group. However, clinical features of PCOS including gonadotropic hormone (FSH), hyperandrogenism, and dyslipidemia were significantly correlated with variants of FSHR. The present study concludes that rs6165 and rs6166 were significantly related to clinical features of PCOS, regardless of providing direct disease risk.

Association analysis of LHCGR variants and polycystic ovary syndrome in Punjab: a case-control approach.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder that affects women at their child bearing age. The exact etiology is uncertain, however the involvement of multiple genes and environmental interactions has been proposed for the advancement of PCOS. The aim of present study was to evaluate the association of LHCGR variants (rs2293275 and rs12470652) with PCOS in Punjab. METHODS: The present case-control study comprised a total of 743 women (421 PCOS cases and 322 healthy controls). Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP). Biochemical analysis was carried out to measure the levels of cholesterol, High-density lipoprotein (HDL), Low-density lipoprotein (LDL), Very low-density lipoprotein (VLDL), triglycerides, testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). All the statistical analysis was done using SPSS (version21, IBM SPSS, NY, USA). RESULTS: The mutant genotype (AA) and mutant allele (A) of rs2293275 conferred 1.7 and 1.3 fold risk, respectively and mutant allele (C) of rs12470652 conferred 2.3 fold risks towards PCOS progression. Levels of cholesterol and triglycerides were elevated and HDL levels were lower in PCOS cases as compared to controls. Total testosterone and luteinizing hormone levels were also found to be higher in PCOS cases. CONCLUSION: Our study postulated that LHCGR variants are playing a cardinal role in the progression of PCOS and can be used to assess the risk of PCOS in women of reproductive age.

Cytogenetic analysis in couples with recurrent miscarriages: a retrospective study from Punjab, north India.

Human reproduction is considered as the most inefficient event as ~15-20% of human pregnancies end in miscarriage and in the product of miscarriages, chromosomal anomalies are a common occurrence. The aim of the present retrospective study was to assess the frequency of chromosomal aberrations in couples with recurrent miscarriages in the region of Punjab and to compare with worldwide frequencies. In this study, a total of 440 cases were referred between the period 1995-2015. After lymphocyte culturing, giemsa-trypsin banding was done for each case to assess the chromosomal anomalies. The frequency of chromosomal aberrations among couples was found to be 3.41% in our study. Among these aberrations, balanced reciprocal translocations formed the largest group with 60% anomalies. We would conclude that clinicians should understand the importance of chromosomal analysis in these couples and refer them for karyotyping after two miscarriages to rule out the possible genetic cause of recurrent miscarriages.

Association of tumor necrosis factor-alpha 308G/A polymorphism with recurrent miscarriages in women.

BACKGROUND: Recurrent miscarriage (RM) is the most common pregnancy loss in the first trimester affecting approximately 0.5-2% of women. It is a heterogeneous condition and remains an enigma as the underlying cause is still difficult to track down. AIM: This study was aimed to investigate the distribution of tumor necrosis factor-alpha (TNF-α) 308G/A polymorphism and its association with RM in females. The comparative picture was also demonstrated by comparing genotyping results with healthy control women having no history of miscarriage. METHODS: This clinical study was conducted among 115 women aged 21-44 years with history of recurrence of miscarriage. The samples were collected from women attending the outpatient departments of various hospitals, nursing homes, and infertility clinics of this region. In the present study, 111 fertile healthy women aged 24-46 years with at least one live birth and no history of miscarriage were also included. RESULTS: Mean age of women with RM was found to be 28 ± 5.6 years by recall method, whereas it was found to be 30 ± 7.4 in context to healthy women with no history of pregnancy loss. In the present study, 66% of women with RM had homozygous wild type genotype (GG) while 30% and 4% of women had heterozygous (GA) and homozygous mutant genotype (AA), respectively. Among control group, 79%, 16%, and 5% of women showed GG, GA, and AA genotype, respectively. CONCLUSION: The current study supports the concept of TNF-α 308G/A variant in particular with reproductive failure, GG and GA alleles showing 1-fold risk association with RM (odds ratio: 1.86 and 1.43, respectively).