Association of luteinizing hormone chorionic gonadotropin receptor gene polymorphism (rs2293275) with polycystic ovarian syndrome.

BACKGROUND: Polycystic ovaries and irregular menstruation/anovulation are important diagnostic criteria along with hyperandrogenism as per the Androgen Excess Society-2006 criteria for polycystic ovarian syndrome (PCOS). In the etiopathogenesis of PCOS, one of the candidate genes causing ovarian failure is the luteinizing hormone (LH) chorionic gonadotropin hormone receptor (LHCGR). Our aim was to study the association of LHCGR polymorphism (rs2293275) with PCOS in our study population. MATERIALS AND METHODS: Genetic case-control study from multiple gynecological centers from Hyderabad, a cosmopolitan city in South India. The study involved 204 women with PCOS and 204 healthy, sex-, and age-matched controls. Anthropometric and biochemical profiles were taken in a well-designed pro forma. Isolation of deoxyribonucleic acid (DNA) and genotype analysis were done for the entire study population using the polymerase chain reaction-restriction fragment length polymorphism method followed by 12% polyacrylamide gel electrophoresis. RESULTS: In this study, we have demonstrated an association between LHCGR (rs2293275) polymorphism and PCOS. The frequency of the G allele was 0.60 in PCOS and 0.49 in controls (odds ratio [OR] 1.531, confidence interval [CI] 1.16-2.01, and p-value=0.0026), which indicates that the G allele is associated with PCOS in our population. The GG genotype conferred a significant risk of developing PCOS (OR 3.36, CI 1.96-5.75, and p-value<0.0001). We found a significant association of the GG allele with body-mass index, waist to hip ratio, insulin resistance, LH, and LH/follicle-stimulating hormone (FSH) ratio in PCOS when compared with controls. The AA allele showed high basal FSH levels. CONCLUSIONS: This study suggests that LHCGR (rs2293275) polymorphism is associated with PCOS and could be used as a relevant molecular marker to identify women with the risk of developing PCOS in our population and may provide an understanding about the etiology of PCOS.

Tumor necrosis factor-alpha and polycystic ovarian syndrome: a clinical, biochemical, and molecular genetic study.

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) appears to be linked with hyperandrogenism (HA), increased insulin resistance (IR), and obesity (Ob), which were common features noted with polycystic ovarian syndrome (PCOS). Our aim was to study the role of TNF-α in the pathogenesis of IR and Ob in PCOS, as well as a C850T (rs1799724) polymorphism in the promoter region of the TNF-α gene, in a group of 204 PCOS patients and 204 age-matched healthy controls. RESULTS: Significant differences were observed between PCOS patients and controls. All the PCOS had elevated body mass index, waist circumference, waist-to-hip ratio, fasting insulin, homeostatic model assessment (HOMA) score, and serum TNF-α when compared with controls (p<0.05). Genotype distribution for the C-850T polymorphism was observed with the frequency of the variant T allele being 0% in the PCOS group and 9% in the control group (p=0.0032). CONCLUSIONS: In conclusion, our present results suggest that the TNF-α system might contribute to the pathogenesis of HA, Ob, and IR in PCOS independent of a polymorphism of the TNF-α C850T (rs1799724) in our population.

Anthropometric and Biochemical Characteristics of Polycystic Ovarian Syndrome in South Indian Women Using AES-2006 Criteria.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine conditions affecting women of reproductive age with a prevalence of approximately 5-10% worldwide. PCOS can be viewed as a heterogeneous androgen excess disorder with varying degrees of reproductive and metabolic abnormalities, whose diagnosis is based on anthropometric, biochemical and radiological abnormalities. To our knowledge, this is the first study investigating the anthropometric, biochemical and ultrasonographic characteristics of PCOS in Asian Indians of South India, using the Androgen Excess Society (AES-2006) diagnostic criteria. OBJECTIVES: To assess anthropometric, biochemical and ultrasonographic features of PCOS subgroups and controls among South Indian women using the AES-2006 criteria. MATERIALS AND METHODS: Two hundred and four women clinically diagnosed with PCOS, and 204 healthy women controls aged 17 to 35 years were evaluated. PCOS was diagnosed by clinical hyperandrogenism (HA), irregular menstruation (IM), and polycystic ovary (PCO). PCOS was further categorized into phenotypic subgroups including the IM+HA+PCO (n = 181, 89%), HA+PCO (n = 23, 11%), IM+HA (n = 0), and also into obese PCOS (n = 142, 70%) and lean PCOS (n = 62, 30%) using body mass index (BMI). Anthropometric measurements and biochemical characteristics were compared among the PCOS subgroups. RESULTS: The PCOS subgroups with regular menstrual cycles (HA+PCO), had more luteinizing hormone (LH), follicle stimulating hormone (FSH), fasting glucose, fasting insulin, and high insulin resistance (IR) expressed as the Homeostasis Model Assessment (HOMA) score, compared with the IM+HA+PCO subgroups and controls. Similarly, the obese PCOS had high BMI, waist to hip ratio (WHR), fasting glucose, LH, LH/FSH, fasting insulin, HOMA score (IR), and dyslipidemia, compared with lean PCOS and controls. Unilateral polycystic ovary was seen in 32 (15.7%) patients, and bilateral involvement in 172 (84.3%) patients. All the controls showed normal ovaries. CONCLUSIONS: Anthropometric, biochemical, and ultrasonographic findings showed significant differences among PCOS subgroups. The PCOS subgroups with regular menstrual cycles (HA+PCO), had high insulin resistance (IR) and gonadotropic hormonal abnormalities, compared with the IM+HA+PCO subgroups and controls.

Biomarkers for the management of pre-eclampsia in pregnant women.

Pre-eclampsia (PE) is a pregnancy related disorder characterized by hypertension and proteinuria noticeable after 20 wk of gestation. It is a leading cause of maternal and foetal mortality and morbidity worldwide. The aetiology of the disease is unknown, but recent studies have revealed that this disorder appears to originate in placenta and is characterized by widespread maternal endothelial dysfunction. Till date, delivery of placenta is the only cure for the disease. So, there is a need for the identification of highly specific and sensitive biochemical markers that would allow early identification of patients at risk and thus help in providing proper prenatal care. Several promising biomarkers have been proposed, alone or in combination, that may help in predicting women who are likely to develop PE. Maternal serum concentrations of these biomarkers either increase or decrease in PE during gestation. This review focuses on the various biomarkers available and their utility in predicting pre-eclampsia.

Estrogen receptor-alpha gene (T/C) Pvu II polymorphism in endometriosis and uterine fibroids.

Endometriosis and fibroids are estrogen-dependent benign pathologies of the uterus, which account for infertility and pelvic pain along with dysmenorrhea in women. Suppression of the disease and recurrence after discontinuing hormone therapy strongly suggests that these are responsive to hormones, especially estrogen, which acts via its receptor. A T/C SNP in intron 1 and exon 2 boundary of estrogen receptor (ER) alpha gene recognized by PvuII enzyme has been associated with several female pathologies like breast cancer, osteoporosis, endometriosis and fibroids in various ethnic groups. The aim of the present study was to assess this ER alpha T/C polymorphism in endometriosis and fibroid patients from Asian Indian population. Genomic DNA was isolated from 367 women, who included 110 cases of endometriosis, 142 cases of uterine fibroids and 115 healthy age matched women volunteers. PCR was carried out to amplify ER alpha gene followed by restriction digestion with Pvu II. Results indicate a significant association of C allele with both endometriosis [OR=2.6667, 95% CI=1.4166 to 5.0199; p < 0.05] and fibroids [2.0833, 95% CI=1.1327 to 3.8319; p < 0.05]. Further studies are needed in larger population to establish ERalpha C allele as a risk marker for endometriosis and fibroids in Asian Indian women. Ethnicity, race, diet etc may play a role in susceptibility to endometriosis and fibroids and further studies are warranted in this area.

Polymorphic (CAG)n repeats in the androgen receptor gene: a risk marker for endometriosis and uterine leiomyomas.

BACKGROUND: Endometriosis and uterine leiomyomas are leading hormone responsive, benign uterine disorders responsible for high morbidity in women of reproductive age group. A polymorphic (CAG)n repeat length located in exon 1 of the androgen receptor (AR) gene has been proposed as a risk marker for both endometriosis and leiomyomas in some ethnic groups. The present study was carried out to assess the frequency of AR (CAG)n repeat polymorphism as a risk marker for endometriosis and uterine leiomyomas in Asian Indian women. METHODS: DNA was isolated from peripheral blood samples of 331 subjects, which include 90 endometriosis cases, 140 cases of leiomyomas and 101 healthy age- and sex-matched controls. PCR was carried out to amplify exon 1 of the AR gene. All the PCR amplicons were analysed initially on 2% agarose gel electrophoresis, followed by bidirectional sequencing to calculate the number CAG repeats in individuals. RESULTS: The CAG repeat ranges detected in endometriosis cases were 4-33 (Mode-19) and in leiomyomas cases 5-34 (Mode-20), whereas in controls it was 5-34 (Mode-22). A distinct variation was observed in the three groups at 14, 18, 19, 20 and 22 (CAG)n repeats, which were statistically analyzed using chi-square and odds ratio tests. 19 CAG repeats were found to be higher in endometriosis cases (19.09%) when compared with controls (9.04%), while 20 CAG repeats were higher in leiomyomas cases (14.02%) compared to controls (6.14%). A statistically significant (P < 0.05) association was observed in 19 and 20 CAG repeats in endometriosis and leiomyomas, respectively. CONCLUSION: This is the first report from an Asian Indian population proposing that 19 and 20 CAG repeats of the AR gene are associated with endometriosis and leiomyoma and can be regarded as high-risk markers.