title: Genetic variants of the HSD11B1 gene promoter may be protective against polycystic ovary syndrome.
abstract: The HSD11B1 gene encodes the type 1 isoform of the 11-β-hydroxysteroid dehydrogenase that is responsible for the regeneration of glucocorticoids from hormonally-inactive metabolites into active forms in a tissue-specific manner. Altered activity of the enzyme, and certain genetic variants of the HSD11B1 gene, has been associated with various metabolic morbidities. In this study, our aim was to systematically test the potential role of the HSD11B1's single nucleotide polymorphisms (SNPs) in polycystic ovary syndrome (PCOS). Nine HSD11B1 SNPs were selected and genotyped using Taqman SNP assays on real-time PCR in a group of PCOS patients (n = 58) and in age-matched healthy controls (n = 64). Genotype-phenotype correlations were determined and haplotype analysis was performed. An in silico prediction for potential transcription factor binding sites was also performed. Of the 5 promoter SNPs, 3 (rs760951; rs4844880; rs3753519) were less frequent in the PCOS group compared to healthy controls. SNPs rs4844880 and rs3753519 were in a complete linkage and the mutant haplotype (AA) was less frequent in the PCOS group. No association between HSD11B1 variants and clinical, pathological findings was observed in patients, but in healthy women the rs4844880 and the AA haplotype were associated with higher levels of homeostasis model assessment of beta cell function. The polymorphic form of the rs4844880 was predicted to bind Pbx-1. Promoter SNPs of the HSD11B1 gene might exert a potential genetic protective role against the development of PCOS, possibly via their beneficial effect on carbohydrate homeostasis due to facilitation of insulin efflux from pancreatic beta-cells.
authors: 2nd Department of Medicine, Semmelweis University, Szentkirályi 46, Budapest, 1088, Hungary, grolmusz.vince@med.semmelweis-univ.hu.
authors: Vince Kornél
authors: VK
authors: Grolmusz
authors: Orsolya Dóra
authors: OD
authors: Acs
authors: Karolina
authors: K
authors: Feldman-Kovács
authors: Ágnes
authors: Á
authors: Szappanos
authors: Balázs
authors: B
authors: Stenczer
authors: Tibor
authors: T
authors: Fekete
authors: György
authors: G
authors: Szendei
authors: Péter
authors: P
authors: Reismann
authors: Károly
authors: K
authors: Rácz
authors: Attila
authors: A
authors: Patócs
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics*; D000328:Adult; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D055815:Young Adult
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human