Androgen levels and metabolic parameters are associated with a genetic variant of F13A1 in women with polycystic ovary syndrome

• Published in: Gene 2012-08, Vol.504 (1), p.133-139
• Main Authors: Schweighofer, N., Lerchbaum, E., Trummer, O., Schwetz, V., Pilz, S., Pieber, T.R., Obermayer-Pietsch, B.
• Format: Article
• Language: English
• Subjects: Adult; Androgens; Androgens - metabolism; Blood coagulation; Blood pressure; Body Composition; Body Mass Index; Case-Control Studies; Cholesterol; Cohort Studies; Factor XIIIa - genetics; Female; Globulins; Glucose; HDL; Humans; Hyperandrogenism - genetics; Infertility; Insulin; Insulin Resistance; Lipoproteins (high density); Obesity; Obesity - etiology; PCOS; polycystic ovary syndrome; Polycystic Ovary Syndrome - complications; Polycystic Ovary Syndrome - genetics; Polycystic Ovary Syndrome - metabolism; Polymerase Chain Reaction; Polymorphism, Single Nucleotide - genetics; Prognosis; Sex hormones; Single-nucleotide polymorphism; Testosterone; Testosterone - blood; Triglycerides
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2012.04.050

The polycystic ovary syndrome (PCOS), characterized by hyperandrogenism, is one of the most common hormonal disorders among premenopausal women and is associated with infertility, obesity, and insulin resistance. Accumulating evidence suggests a role of the blood coagulation factor gene F13A1 in obesity (GeneBank ID: NM_000129.3). The aim of this study was to investigate the association of intronic allelic variants of the F13A1 gene with PCOS susceptibility and metabolic parameters in lean and obese PCOS women. In a case–control study, we determined an intronic F13A1 single nucleotide polymorphism (SNP) (dbSNP ID: rs7766109) in 585 PCOS and 171 control women and tested for PCOS susceptibility and associations with anthropometric, metabolic and hormonal parameters. Genotype frequencies of the F13A1 SNP rs7766109 were equivalent in PCOS and control women. In PCOS women, F13A1 gene variants were significantly associated with body mass index (BMI) (p=0.013), systolic blood pressure (p=0.042), insulin response (AUCins) (p=0.015), triglycerides (TG) (p=0.001), and high density lipoprotein cholesterol (HDL) (p=0.012). In the subgroup of obese PCOS women free androgen index (FAI), free testosterone and sex hormone binding globulin (SHBG) as well as glucose measurements showed a significantly different pattern across F13A1 gene variants (p=0.043; p=0.039 and p=0.013, respectively). We report for the first time an association of the F13A1 SNP rs7766109 with BMI, androgens, and insulin resistance in PCOS women. Further studies are needed to confirm our findings and to evaluate whether F13A1 is causally involved in the pathogenesis of PCOS related metabolic and hormonal disturbances. ► We investigate a genetic variant (A/G) of F13A1 in lean and obese PCOS women. ► Obese PCOS women carrying the G allele have elevated free testosterone. ► Obese PCOS women with G allele show impaired insulin response to glucose load. ► Lean PCOS women with the G/G genotype have higher BMI and systolic blood pressure. ► Lean PCOS women with the G/G genotype show negative changes in their lipid profile.