Abstract
BackgroundFat mass and obesity-associated gene (FTO) has been associated with obesity, especially the common variant rs9939609. Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder and over 50% of patients are overweight/obese. Thus FTO is a potential candidate gene for PCOS but their relationship is confusing and remains to be clarified in different population with a large sample size. MethodThis study was performed adopting a two-stage design by genotyping SNP rs9939609. The first set comprise of 741 PCOS and 704 control subjects, with data from our previous GWAS. The second phase of replication study was performed among another independent group of 2858 PCOS and 2358 control subjects using TaqMan-MGB probe assay. All subjects are from Han Chinese. ResultsThe less meaningful association of FTO rs9939609 and PCOS discovered in GWAS (P = 2.47E-03), was further confirmed in the replication study (P = 1.86E-09). Using meta-analysis, the P-meta value has reached 6.89E-12, over-exceeding the genome-wide association level of 5.00E-8. By combination, the P value was 1.26E-11 and after BMI adjustment it remained significant(P = 1.82E-06). To further elucidate whether this association is resulted from obesity or PCOS per se, the samples were divided into two groups–obese and non-obese PCOS, and the results were still positive in obese group (P obese = 5.81E-05, OR = 1.55), as well as in non-obese PCOS group (P non-obese = 7.06E-04, OR = 1.28). ConclusionVariant rs9939609 in FTO is associated with PCOS in Chinese women, not only in obese PCOS subjects, but also in non-obese cases.
Highlights
Polycystic ovary syndrome (PCOS) is a complex endocrinemetabolic disease affecting 6–8% women of reproductive age [1]
The less meaningful association of Fat mass and obesity-associated gene (FTO) rs9939609 and PCOS discovered in GWAS (P = 2.47E-03), was further confirmed in the replication study (P = 1.86E-09)
To further elucidate whether this association is resulted from obesity or PCOS per se, the samples were divided into two groups–obese and non-obese PCOS, and the results were still positive in obese group (P obese = 5.81E-05, Odd ratios (ORs) = 1.55), as well as in non-obese PCOS group (P non-obese = 7.06E-04, OR = 1.28)
Summary
Polycystic ovary syndrome (PCOS) is a complex endocrinemetabolic disease affecting 6–8% women of reproductive age [1]. Characterized by clinical and/or biochemical androgen excess, ovulatory dysfunction and polycystic ovaries, PCOS patients is associated with an increased risk of overweight/obesity, insulin resistance and type 2 diabetes mellitus (T2DM) [1,2,3,4]. Over 50% PCOS cases are overweight/obese [5]. Evidence implies obesity, interacting with T2DM and endocrine disorders, is an important factor in the etiology of PCOS [6,7]. Family-based and case-control association studies suggest genetic factors contribute to both obesity and PCOS, which implicates a shared genetic predisposition in their concurrence [9,10,11]. Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder and over 50% of patients are overweight/obese. FTO is a potential candidate gene for PCOS but their relationship is confusing and remains to be clarified in different population with a large sample size
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