Association of MEP1A gene variants with insulin metabolism in central European women with polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) shows not only hyperandrogenemia, hirsutism and fertility problems, but also metabolic disturbances including obesity, cardiovascular events and type-2 diabetes. Accumulating evidence suggests some degree of inflammation associated with prominent aspects of PCOS. We aimed to investigate the association of genetic variants 3'UTR rs17468190 (G/T) of the inflammation-associated gene MEP1A (GenBank ID: NM_005588.2) with metabolic disturbances in PCOS and healthy control women. Genetic variants rs17468190 (G/T) of MEP1A gene were analyzed in 576 PCOS women and 206 controls by using the Taqman fluorogenic 5'-exonuclease assay. This polymorphism was tested for association with anthropometric, metabolic, hormonal, and functional parameters of PCOS. There was a borderline significant difference in genotype distribution between PCOS and control women (p=0.046). In overweight/obese PCOS patients, the variants rs17468190 (G/T) in the MEP1A gene are associated with glucose and insulin metabolism. In a dominant model, the GG genotype of the MEP1A gene was more strongly associated with insulin metabolism in overweight/obese PCOS women (body mass index, BMI>25 kg/m(2)), than in GT+TT genotypes. The MEP1A GG-carriers showed a significantly increased homeostatic model assessment - insulin resistance (HOMA-IR) (p=0.003), elevation of fasting insulin (p=0.004) and stimulated insulin (30 min, p<0.001; 60 min, p=0.009; 120 min, p=0.009) as well as triglyceride (p=0.032) levels. MEP1A is a possible target gene for disease modification in PCOS. It might contribute to the abnormalities of glucose metabolism and insulin sensitivity and serve as a diagnostic or therapeutic target gene for PCOS.

Keywords: 25(OH)D; 25-hydroxyvitamin D; 3′ untranslated regions; 3′UTR; ANOVA; ASRM; American Society for Reproductive Medicine; BMI; DHEAS; DNA; EDTA; ESHRE; European Society of Human Reproduction and Embryology; FAI; GNRH1; HDL; HOMA-IR; IR; International System of Units; LDL; Lipids; Meprin 1A; Metabolic; NCBI; NICHD; National Center for Biotechnology Information; National Institute of Child Health and Human Development; Obesity; PASW; PCOS; PTH; Polymorphism; Predictive Analytics Software; QChol/HDL; SHBG; SI; SNP; TG; TT; WHR; analysis of variance; body mass index; dehydroepiandrosterone sulfate; deoxyribonucleic acid; ethylenediaminetetraacetate; fT; free androgen index; free testosterone; gonadotropin-realeasing hormone; high density lipoprotein; homeostatic model assessment-insulin resistance; insulin resistance; low density lipoprotein; parathyroid hormone; polycystic ovary syndrome; quotient total cholesterol to HDL; sex hormone-binding globulin; single nucleotide polymorphism; total testosterone; triglycerides; waist-to-hip ratio.