ESR1, HK3 and BRSK1 gene variants are associated with both age at natural menopause and premature ovarian failure.
ESR1, HK3 and BRSK1 gene variants are associated with both age at natural menopause and premature ovarian failure.
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ESR1、HK3 和 BRSK1 基因变异与自然绝经年龄和卵巢早衰有关
DOI：
10.1186/1750-1172-7-5
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发表时间：
2012-01-17
影响因子：
3.7
通讯作者：
Chen ZJ
中科院分区：
文献类型：
--
作者：
Qin Y;Sun M;You L;Wei D;Sun J;Liang X;Zhang B;Jiang H;Xu J;Chen ZJ
研究背景卵巢早衰（POF）是一种受多种遗传因素影响的复杂异质性疾病。许多旨在鉴定POF易感基因座的候选基因研究已经发表，但大多数阳性发现尚未在后续研究中得到证实。我们试图确定是否与自然绝经年龄（AANM）或绝经早期（EM）的序列变异，以及对POF.MethodsOur研究的遗传易感性进行了371无关的原发性POF妇女和800名妇女对照组，所有中国汉族。三十六个单核苷酸多态性从以前的全基因组关联研究（GWAS）负责AANM或EM和3个额外的单核苷酸多态性在ESR 1，和2个额外的单核苷酸多态性在PTHB 1进行了测试，使用Sequenom MassARRAY iPLEX平台进行genotyping.ResultsThree单核苷酸多态性-rs 2278493在香港3，rs 2234693在ESR 1和rs 12611091在BRSK 1-显示名义上显着关联POF。因此，一个合理的关系可能存在ESR 1，BRSK 1，HK 3和POF.ConclusionsThis最大的关联研究进行，以确定POF和AANM/EM之间的相关性揭示了三个显着的SNP（rs 2278493，rs 2234693，和rs 12611091）。所有这些不仅与AAWM和EM有关，而且与POF有关。了解POF和AANM/EM之间的共同遗传易感性将为解开卵巢储备和卵母细胞老化过程中涉及的遗传机制提供新的切入点。
BackgroundPremature 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.MethodsOur 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.ResultsThree 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.ConclusionsThis 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.
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影响因子：
44.1
作者：
Shi, YY;He, L
通讯作者：
He, L
影响因子：
6.7
作者：
Bretherick, Karla L.;Hanna, Courtney W.;Robinson, Wendy P.
通讯作者：
Robinson, Wendy P.
影响因子：
4.8
作者：
Lu, R;Niida, H;Nakanishi, M
通讯作者：
Nakanishi, M
DOI：
10.1196/annals.1429.019
发表时间：
2008-01-01
期刊：
MENSTRUAL CYCLE AND ADOLESCENT HEALTH
影响因子：
--
作者：
Simpson, Joe Leigh
通讯作者：
Simpson, Joe Leigh
影响因子：
6.1
作者：
Tibiletti, MG;Testa, G;Crosignani, PG
通讯作者：
Crosignani, PG