Replication study of RAD54B and GREB1 polymorphisms and risk of PCOS in Han Chinese

Abstract

A previous genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) identified several susceptibility loci, with P-values about 10−5. In the present study, an independent cohort was used for a replication study to evaluate the association of RAD54B and GREB1 with polycystic ovary syndrome (PCOS) in the Han Chinese population. Four single-nucleotide polymorphisms (SNP), rs2930961 (RAD54B), rs12470971, rs11686574 and rs6740248 (GREB1), were genotyped in 1124 PCOS patients and 1067 healthy controls from the Han Chinese population. Real-time quantitative PCR by TaqMan-MGB probe assay was applied for genotyping. The allele and genotype frequencies of these four SNP were not significantly different in the replication cohort. However, the minor allele frequency of rs2930961 was significantly different in hyperandrogenism of PCOS. After meta-analysis by combining the results of these two studies, there was a non-significant trend for the association of rs2930961 (RAD54B) with PCOS. RAD54B and GREB1 gene polymorphisms may not be associated with PCOS in the Han Chinese population. Nevertheless, RAD54B may contribute to hyperandrogenism in PCOS patients.Polycystic ovary syndrome (PCOS) is a heterogeneous endocrinopathy. Contribution of different genetic factors to the development of the disease is now widely accepted. To discover new candidate genes, based on a previously published genome-wide association study (GWAS), a replication study was conducted. The genes for RAD54 homologue B (RAD54B) and growth regulation by oestrogen in breast cancer 1 (GREB1), which are important for meiotic and mitotic recombination (RAD54B) and hormone signal target (GREB1), were found to be associated with PCOS in the previous GWAS. However, this association was not confirmed in the current replication study. Genotype–phenotype analysis shows RAD54B is associated with hyperandrogenism of PCOS. This finding provides new insight for GWAS data related to PCOS.