ESR1、HK3 和 BRSK1 基因突变与自然绝经年龄和卵巢早衰均有关。
ESR1, HK3 and BRSK1 gene variants are associated with both age at natural menopause and premature ovarian failure.
机构信息
Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, The Key laboratory for Reproductive Endocrinology of Ministry of Education, Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
出版信息
Orphanet J Rare Dis. 2012 Jan 17;7:5. doi: 10.1186/1750-1172-7-5.
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 rs12611091 in 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 rs12611091). All are associated with not only AAWM and EM but also POF. Insights into shared genetic susceptibility between POF and AANM/EM will provide novel entry points for unraveling genetic mechanism involved in ovarian reserve and oocyte aging processes.
背景
卵巢早衰（POF）是一种复杂的异质性疾病，受多种遗传因素的影响。已经发表了许多旨在确定 POF 易感性基因座的候选基因研究，但大多数阳性发现并未在后续研究中得到证实。我们试图确定以前与自然绝经年龄（AANM）或早期绝经（EM）相关的序列变异是否也与 POF 的遗传易感性有关。
方法
我们的研究对象是 371 名无相关原因的 POF 女性和 800 名中国汉族女性对照。使用 Sequenom MassARRAY iPLEX 平台，对之前与 AANM 或 EM 相关的 36 个全基因组关联研究（GWAS）的 SNP、ESR1 中的 3 个额外 SNP 和 PTHB1 中的 2 个额外 SNP 进行基因分型。
结果
三个 SNP - HK3 中的 rs2278493、ESR1 中的 rs2234693 和 BRSK1 中的 rs12611091 - 与 POF 呈名义上的显著关联。因此，ESR1、BRSK1、HK3 和 POF 之间可能存在一种合理的关系。
结论
这项旨在确定 POF 与 AANM/EM 之间相关性的最大关联研究揭示了三个显著的 SNP（rs2278493、rs2234693 和 rs12611091）。所有这些 SNP 不仅与 AAWM 和 EM 相关，而且与 POF 相关。对 POF 和 AANM/EM 之间共享遗传易感性的深入了解将为揭示卵巢储备和卵母细胞衰老过程中涉及的遗传机制提供新的切入点。
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