Abstract
BackgroundPCOS is a common disorder of women due to genetic, endocrine and environmental effects that manifests from puberty. The rs9939609 variant of fat mass and obesity associated (FTO) gene is linked to metabolic derangement in PCOS. We previously identified FTO (rs9939609) as a susceptibility locus for PCOS among Sri Lankan women and also explored the role of kisspeptin. Associated factors of the FTO candidate gene among South Asians with PCOS are unknown.MethodsThis study aimed to determine the association between FTO (rs9939609) polymorphism with clinical (BMI, acanthosis nigricans, hirsutism) and biochemical (serum kisspeptin and testosterone levels) characteristics of PCOS in a cohort of Sri Lankan women. Genetic and clinical data including serum kisspeptin and testosterone concentrations of our previously reported cases (n = 55) and controls (n = 110) were re-analyzed, specifically for an association with rs9939609 variant of FTO gene.ResultsLogistic regression analysis (AA – OR = 5.7, 95% CI = 2.41–13.63, p < 0.05) and genetic inheritance analysis (AA – OR = 5.49, 95%CI = 2.34–12.88, p < 0.05) showed that FTO (rs9939609) polymorphism is significantly associated with PCOS and its metabolic manifestations. Serum testosterone was significantly higher in affected women with mutant genotypes (AA+AT) than with the normal allele (TT) (p < 0.05). Although serum kisspeptin was higher in subjects with PCOS and mutant alleles than controls, this difference was not significant (p > 0.05).ConclusionFTO gene variant rs9939609 is associated with hyperandrogenemia and metabolic manifestations of PCOS among women of Sri Lankan descent with the well-characterized phenotype. Serum kisspeptin and the FTO genotypes lack a significant association when adjusted for confounders.
Highlights
Polycystic ovary syndrome (PCOS) is a common disorder of women due to genetic, endocrine and environmental effects that manifests from puberty
We aimed to identify any association of fat mass and obesity associated (FTO) gene variant rs9939609 with clinical and hormonal characteristics of PCOS among young Sri Lankan women with well characterized PCOS
Our model showed that body mass index (BMI), serum kisspeptin levels and FTO rs9939609 (AA) polymorphism remained significant after adjusting for potential confounders
Summary
PCOS is a common disorder of women due to genetic, endocrine and environmental effects that manifests from puberty. The rs9939609 variant of fat mass and obesity associated (FTO) gene is linked to metabolic derangement in PCOS. The well characterized phenotype of PCOS is commonly associated with insulin resistance, obesity and future metabolic/cardiovascular outcomes such as diabetes mellitus, hypertension, carotid artery intimal thickening, The etiology of PCOS is undetermined. It is viewed as a complex trait due to heritable and environmental factors [7,8,9]. In 2007, genome-wide association study identified the fat mass and obesity-associated (FTO) gene as an obesity susceptibility gene [10]. The variant FTO rs9939609 is the most extensively studied, located within the first FTO intron which has two alleles, A and T, the former linked to an increased risk for both obesity and type 2 diabetes mellitus [12]
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