title: 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.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria. Electronic address: uyen.lam@medunigraz.at.
authors.forename: Uyen D P
authors.initials: UD
authors.lastname: Lam
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lerchbaum
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria.
authors.forename: Natascha
authors.initials: N
authors.lastname: Schweighofer
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria.
authors.forename: Olivia
authors.initials: O
authors.lastname: Trummer
authors.affiliation: Center for Medical Research, Medical University of Graz, Stiftingtalstraße 24, A-8010 Graz, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Eberhard
authors.affiliation: Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty Mannheim, University of Heidelberg, Ludolf-Krehl-Straße 7-11, D-68167 Mannheim, Germany; Instituto de Saúde Coletiva, Federal University of Bahia, Rua Basílio da Gama, Campus Universitário Canela, Cep: 40.110-040 Salvador, BA, Brazil.
authors.forename: Bernd
authors.initials: B
authors.lastname: Genser
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pieber
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Obermayer-Pietsch
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D001317:Austria; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000378:metabolism; D050177:Overweight / Q000235:genetics / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D007328:Insulin; D014280:Triglycerides; D008666:Metalloendopeptidases; C053833:meprin A; D005947:Glucose
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