Interaction between common variants of FTO and MC4R is associated with risk of PCOS

Abstract

BackgroundPolycystic ovary syndrome (PCOS) is a common and complex endocrine-metabolic disease. One of the well-documented characteristics of PCOS is obesity or overweightness. It is possible to be genetically predisposed to becoming obese or overweight, and several potentially causative single nucleotide polymorphisms (SNPs), such as rs9939609 (A/T) in the fat mass, and obesity-associated gene (FTO) and rs17782313 (T/C) in the melanocortin-4 receptor gene (MC4R), have been investigated. Further investigation of association between obesity-associated SNPs and PCOS susceptibility will contribute to a better understanding of the disease.MethodsIn the present study, we enrolled 733 patients with PCOS and 892 control subjects. The common variants FTO rs9939609 and MC4R rs17782313 were genotyped and their relationship with obesity-related traits was evaluated.ResultsRs9939609 and rs17782313 are associated with PCOS and obesity-related traits and profiles. The association found between PCOS and FTO rs9939609 (p = 0.0302) was attenuated after adjustment for BMI (p = 0.187). MC4R rs17782313 did not confer an increased risk for PCOS (p = 0.368) even after adjustments (p = 0.715). Interestingly, the interaction of FTO and MC4R polymorphisms was more significantly associated with PCOS (p = 0.031, adjusted for age and BMI). The FTO variant rs9939609 is associated with Chinese women with PCOS; however, this association is affected by BMI.ConclusionsThe combined pathogenic effect of FTO and MC4R polymorphisms indicates a direct role of the interaction between FTO and MC4R polymorphisms in the development of PCOS.

Phenotype and genotype of polycystic ovary syndrome in Asia: Ethnic differences

“…Thus, polymorphism in the FTO gene was intensively investigated in women with PCOS across ethnicities. Most studies performed in Asian women with PCOS found a significant association between the FTO gene and PCOS . In our Korean study, the FTO gene was not associated with PCOS itself, but each additional copy of the variant allele increased BMI by a mean of 4.8% (95% confidence interval: 1.4–8.3%) or 1.11 kg/m 2 (95% confidence interval: 1.03–1.20 kg/m 2 ) .…”

Cryptotanshinone alleviates polycystic ovary syndrome in rats by regulating the HMGB1/TLR4/NF‑κB signaling pathway

“…Polycystic ovary syndrome (PCOS) is a complex, progressive, refractory gynecological endocrine disease ( 1 ) that clinically manifests as hyperandrogenism with menstrual disorders, infertility, obesity and hemorrhoids ( 2 , 3 ). In addition, PCOS is often linked with various complications, including insulin (INS) resistance, endometrial cancer, hypertension, metabolic syndrome and cardiovascular disease ( 4 – 6 ). PCOS is also a concern for patients of childbearing age because the condition not only causes abnormal menstruation, but also ovulatory dysfunction and infertility ( 7 ).…”

Fat Mass and Obesity Association gene Polymorphism in PCOS Iraqi Women

“…Fat mass and obesity association gene was discovered in 2007 by 3 independent wide genomic association studies in association with polygenic forms of obesity (11). It is highly expressed in neurons of hypothalamus and mesenteric, liver, pancreas and adipose tissues (18,19) to promote the neonatal growth (20) and adults by inducing appetite, food intake, increase hunger /lower satiety and energy balance (21), leading to increase in body weight and hip/circumference ratio (22). FTO gene expands about 40 kb on chromosome 16q12.2, with 9 exons, encoding for 2-oxoglutarate dependent dioxygenase with DNA/RNA demethylase activity (23).…”