Association of variants in the fat mass and obesity associated (FTO) gene with polycystic ovary syndrome

Abstract

Aims/hypothesis Variants in the fat-mass and obesityassociated gene (FTO) influence susceptibility to type 2 diabetes via an effect on adiposity/obesity. Given the important role of obesity in the aetiology of both polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus, our aim was to establish whether FTO variants are also implicated in PCOS susceptibility. MethodsWe performed a genetic association study of FTO variant rs9939609 using case-control analyses, conducted in 463 PCOS patients (geometric mean BMI 27.5 kg/m 2 ) and 1,336 female controls (geometric mean BMI 25.3 kg/ m 2 ) of UK British/Irish origin. We also sought evidence for associations between FTO variation and circulating testosterone levels in 324 UK PCOS patients and 1,000 women from the Northern Finland Birth Cohort of 1966. Outcome Diabetologia (2008) [adjusted]). This association was most evident in obese PCOS patients (PCOS patients below median BMI vs UK controls, p=0.11; above median BMI vs controls, p=2.9× 10 −4 ). No relationship between FTO genotype and androgen levels was seen. Conclusions/interpretation We provide the first evidence that variants that predispose to common obesity also result in altered susceptibility to PCOS, confirming the mechanistic link between these conditions. The predominant effect of FTO variants on PCOS susceptibility is probably mediated through adiposity.

Association between Fat Mass and Obesity Associated (FTO) Gene Polymorphism (rs9939609) and Polycystic Ovary Syndrome (PCOS): A Sri Lankan Study

“…Furthermore, present study showed significant correlation between FTO gene polymorphism and BMI in PCOS group. This finding is consistent with former studies by Barber et al, (2008) and Farhan et al, (2015).…”

“…Recruitment of Subjects: Women whose symptoms manifested from adolescent years (11)(12)(13)(14)(15)(16)(17)(18)(19) years WHO), with all 3 diagnostic criteria present when aged between 16-19 years (Anovular PCOS, hyperandrogenism and polycystic ovaries on ultrasound) were recruited as cases. Women who are asymptomatic, non-androgenic, normal cycling, in whom PCOS was objectively excluded by clinical, biochemical and ultrasound assessment, were recruited as controls.…”

Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance

“…5 Further evidence to corroborate the association between PCOS and obesity were provided by our own group, revealing association of variants within the FTO gene and susceptibility for development of PCOS, through effects on fat mass. 6 The association of obesity with PCOS is thought to be important for its development, given that PCOS often becomes clinically manifest in women who gain weight and Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance are genetically predisposed to its development. Furthermore, as previously outlined, the clinical features of PCOS often improve with weight loss.…”

Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance

“…5 Further evidence to corroborate the association between PCOS and obesity were provided by our own group, revealing association of variants within the FTO gene and susceptibility for development of PCOS, through effects on fat mass. 6 The association of obesity with PCOS is thought to be important for its development, given that PCOS often becomes clinically manifest in women who gain weight and Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance s73 are genetically predisposed to its development. Furthermore, as previously outlined, the clinical features of PCOS often improve with weight loss.…”