文献_2012-ESR1, HK3 and BRSK1 gene variants.pdfVIP

Qin et al. Orphanet Journal of Rare Diseases 2012, 7:5 /content/7/1/5 RESEARCH Open Access ESR1, HK3 and BRSK1 gene variants are associated with both age at natural menopause and premature ovarian failure 1 1 1 2 3 4 5 6 7 Yingying Qin , Mei Sun , Li You , Deying Wei , Jielin Sun , Xiaoyan Liang , Bo Zhang , Hong Jiang , Jianfeng Xu and Zi-Jiang Chen1* Abstract Background: Premature ovarian failure (POF) is a complex and heterogeneous disorder that is influenced by multiple genetic components. Numerous candidate gene studies designed to identify POF susceptibility loci have been published, but most positive findings have not been confirmed in follow up studies. We sought to determine if sequence variants previously associated with age at natural menopause (AANM) or early menopause (EM) contribute as well to genetic susceptibility to POF. Methods: Our study was performed on 371 unrelated idiopathic women with POF and 800 women controls, all Chinese Han. Thirty six SNPs from previous genome-wide association studies (GWAS) responsible for AANM or EM and 3 additional SNPs in ESR1, and 2 additional SNPs in PTHB1 were tested using the Sequenom MassARRAY iPLEX platform for genotyping. Results: Three SNPs - rs2278493 in HK3, rs2234693 in ESR1 and rin BRSK1 - showed nominally significant association with POF. Thus, a plausible relationship could exist between ESR1, BRSK1, HK3 and POF. Conclusions: This largest association study undertaken to determine correlation between POF and AANM/EM revealed three significant SNPs (rs2278493, rs2234693, and r. All are associated with not only AAWM and EM but also POF. Insights into shared genetic susceptibility between POF and AANM/EM wil