Background: Hyperandrogenism (HA) is required for diagnosis of polycystic ovary syndrome (PCOS) and it is central to PCOS pathogenesis. Putative mechanisms of hyperandrogenism include disregulation of steroidogenesis, plasma transport and peripheral tissue regulation. Therefore, 5-alpha reductase genes (SRD5A1, SRD5A2), that regulate peripheral tissue conversion of testosterone to more potent dihydrotestosterone are good PCOS candidate genes. The single published study of SRD5A1 and SRD5A in PCOS showed association of several SNPs/haplotypes with PCOS, including rs523349 (Val89Leu in SRD5A2).
Aim: To test association of rs523349 with PCOS and related traits in the Romanian population.
Patients and methods: Two hundred and fifteen PCOS patients (Rotterdam criteria) and 107 eumenorrheic, non-hirsute controls, 1540 years. old, recruited at the C.I. Parhon National Institute of Endocrinology and Elias Emergency University Hospital, Bucharest. rs523349 genotyping was performed by HRM-PCR (Corbett Research), with Razor probes (Primer Design, UK) and validated by direct sequencing.
Results: rs523349 allelic frequency did not differ significantly between PCOS and control (0.72 vs 0.71, P=NS) and was comparable to that observed by Goodarzi et al. rs523349 genotypes were not significantly associated with PCOS. rs523349 (genotypes or allelic frequency) was not associated with PCOS phenotypic/biochemical traits. The statistical power of our study was limited (0.39), but comparable to the original study (0.5).
Conclusions: Our negative association result suggests that SRD5A2, through rs523349, is not a major gene in PCOS genetics in our population. However, exclusion of a true effect will require an adequately-powered study.