Single-nucleotide polymorphism of INS, INSR, IRS1, IRS2, PPAR-G and CAPN10 genes in the pathogenesis of polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is the most common and a complex female endocrine disorder, and is one of the leading cause of female infertility. Here, we aimed to investigate the association of single-nucleotide polymorphism of INS, INSR, IRS1, IRS2, PPAR-G and CAPN10 gene in the pathogenesis of PCOS. A hospital-based, observational case-control study was carried on 169 PCOS and 169 control women in the southern region of India. Genotype was carried out by real-time polymerase chain reaction. A chi-square (χ) test was performed and the genotypes were verified to comply with the Hardy- Weinberg equilibrium. Odds ratio and 95% confidence interval were calculated to assess the relative risk. Comparison of clinical characteristics of women with PCOS and controls reveal an increase in body mass index (BMI), luteinizing hormone / follicle stimulating hormone (LH/FSH) ratio, glucose levels, insulin, testosterone, hirsutism and antral follicular count in PCOS women. The variant rs1801278 (P = 0.002; OR = 2.88; 95% CI = 1.43, 5.80) show an association with PCOS. In the genotypic (P = 0.0002) and allelic models (P = 0.000), significance persisted even after Bonferroni correction. The genotypes of SNPs strongly influence BMI, LH, LH/FSH ratio, ovarian volume and antral follicular count in PCOS women. The study results were suggestive of a positive association between Gly972Arg of IRS1 and PCOS in the south Indian population, while INS, IRS2, PPAR-G and CAPN10 failed to show any association with PCOS in our studied population. Further studies focussing the role of IRS1 are warranted to delineate its implication towards PCOS.

Epidemiology, pathogenesis, genetics & management of polycystic ovary syndrome in India

“…In a small study from Hyderabad, 15 single-nucleotide polymorphisms (SNPs) from nine type 2 diabetes-related genes (such as TCF7L2, IGF2BP2, SLC30A8, HHEX, CDKAL1, CDKN2A, IRS1, CAPN10 and PPAR-γ ) were studied in PCOS women and controls; no significant association was found; the authors cited studies from other ethnic populations and suggested that the non-association might be universal47. Gly972Arg SNP of IRS1 was found to have a positive association with PCOS in a south Indian study population, whereas INS, IRS2, PPAR-γ and CAPN10 failed to show any association in the same study from Chennai48. Insulin receptor gene polymorphism was studied later49, for its association with IR in Indian women with PCOS; the study suggested that CC genotype (C1085T) might be developed as a marker for IR and metabolic complications in Indian women48.…”

The role of AKT and FOXO3 in preventing ovarian toxicity induced by cyclophosphamide

“…MTORC2 is composed of mSIN1 and mLST8 and its core functional component, Rictor. Rictor regulates the functions of its downstream targets Akt, Rho, Rac and Cdc42, which themselves regulate egg cell survival and the construction of the cytoskeleton [ 18 – 21 ].…”

Variant Alleles of the ESR1, PPARG, HMGA2, and MTHFR Genes Are Associated With Polycystic Ovary Syndrome Risk in a Chinese Population: A Case-Control Study

“…This study was approved by the Shanghai Xinhua Hospital Research Ethics Board and all subjects gave their informed consent for inclusion before they participated in the study. Women were excluded if they had been diagnosed with 21-hydroxylase-deficiency, androgen-producing tumors, hyperprolactinemia, non-classical adrenal hyperplasia, Cushing's syndrome, and active thyroid disease, since these conditions likely affect reproductive physiology (19, 29). All the controls were defined as women with normal hormonal status and regular menstrual cycles at intervals of 28–35 days.…”

“…Related studies have been conducted on at least 70 genes, which roles are involved in the main process of this disease, such as steroid synthesis ( CYP11A1 and CYP19A1 ) (15), steroid action ( ESR1, ESR2 , and PGR ) (16), lipid metabolism ( PPARG and MTHFR ) (17–19), insulin action ( HMGA2 ) (20) and embryonic development ( SUMO1P1 ) (21, 22) have been implicated in PCOS. However, the heterogeneity and generalizability of these genetic associations are not enough to explain clearly the considerable genetic susceptibility for this endocrine-metabolic disorder.…”