Association between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome: a systematic review and meta-analysis

Ai Ling Liu,Jie Yin,Hong Yan Xie,Jin Song Hu,Jun Liu,Hui Jun Xie,Cui Ying Peng

doi:10.1186/s12881-017-0452-1

Abstract

BackgroundUp to now, numerous case-control studies have reported the associations between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome (PCOS), however, without a consistent result. Hence we performed current systematic review and meta-analysis to clarify the controversial results.MethodsCase-control studies reporting the relationship of rs9939609 A/T polymorphism and PCOS published before April 2015 were searched in Pubmed database without language restriction. Data was analyzed by Review Manager 5.2.ResultsA total of five studies involving 5010 PCOS patients and 5300 controls were included for further meta-analysis. The results of meta-analysis showed that the FTO gene rs9939609 A/T polymorphism was significantly different between PCOS group and control group in different gene models (For AA + AT vs. TT: OR = 1.41, 95% CI = 1.28–1.55, P < 0.00001. For AA vs. AT + TT: OR = 1.54, 95% CI = 1.25–1.89, P < 0.0001. For AA vs. TT: OR = 1.74, 95% CI = 1.38–2.18, P < 0.00001. For A vs. T: OR = 1.36, 95% CI = 1.25–1.47, P < 0.00001, respectively) suggesting that A allele was a risk factor for PCOS susceptibility. Furthermore, subgroup analysis in Asian and Caucasian ethnicities also found significant association between rs9939609 A/T polymorphism and PCOS (In Asian subgroup: OR = 1.43, 95% CI = 1.29–1.59, P < 0.0001. In Caucasian subgroup: OR = 1.33, 95% CI = 1.08–1.64, P = 0.008)ConclusionThis meta-analysis suggests that rs9939609 A/T polymorphism of FTO gene is associated with PCOS risk, and that A allele is a risk factor for PCOS susceptibility simultaneously.

Highlights

Up to now, numerous case-control studies have reported the associations between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome (PCOS), without a consistent result
Selection of studies Any study included in current meta-analysis must satisfy the following criteria: (a) Case-control studies aimed at investigating the association between FTO rs9939609 polymorphism and PCOS risk. (b) The number of genotypes and allele frequency in cases and controls were respectively available to calculate odds ratio (OR) with 95% confidence interval (CI). (c) Genotypes in control group meet the Hardy − Weinberg equilibrium (HWE) (d) PCOS patients accorded with one diagnose criteria of the following three: 1990 NIH, 2003 Rotterdam, and 2006 AE-PCOS Society [20,21,22]
Based on the inclusion criteria, a total of five studies exploring the association between FTO rs9939609 and PCOS were eligible for current meta-analysis, involving 5010 PCOS patients and 5300 controls [12,13,14,15,16]

Summary

Introduction

Numerous case-control studies have reported the associations between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome (PCOS), without a consistent result. In addition to leading to infertility, PCOS is closely associated with diabetes mellitus type 2, cardiovascular diseases and endometrial carcinoma [1,2,3]. It was firstly reported in 1935 by Stein et al [4], but its etiology still remains ambiguous. It is reasonable to assume that FTO gene might play a role in the pathogenesis of PCOS via BMI and/or obesity. Based on this assumption, many studies have been conducted to research the associations between FTO gene and the risk of PCOS

Methods

Results

Discussion

Conclusion