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.
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