Polymorphisms of estrogen-biosynthesis genes CYP17 and CYP19 may influence age at menarche:: a genetic association study in Caucasian females
Polymorphisms of estrogen-biosynthesis genes CYP17 and CYP19 may influence age at menarche:: a genetic association study in Caucasian females
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DOI：
10.1093/hmg/ddl155
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发表时间：
2006-08-15
影响因子：
3.5
通讯作者：
Deng, Hong-Wen
中科院分区：
文献类型：
--
作者：
Guo, Yan;Xiong, Dong-Hai;Deng, Hong-Wen
月经初潮年龄（AAM）的变化是众所周知的，在很大程度上受到遗传因素的影响，但真正的致病基因仍然在很大程度上不明。由于组织中雌激素暴露幅度的增加启动了月经初潮的发生，因此参与雌激素生物合成的基因是AAM的天然候选基因。我们的研究旨在确定CYP17和CYP19，参与雌激素生物合成的两个关键基因，是否与AAM变异的354个高加索核心家庭的1048名女性。我们对38个SNPs进行了基因分型，并建立了覆盖这两个基因全长的连锁不平衡区和单倍型结构。基于家族和基于人群的统计分析被用于测试与所有单个SNP和单倍型的关联。这两种方法始终检测到CYP19的5个SNP与AAM的显着关联。单倍型分析证实了我们的单SNP结果，显示在块1的单倍型是高度显着的AAM在基于人群的分析。但未发现CYP17与AAM的相关性。我们的研究是第一个提出的重要作用，CYP19 AAM变异在高加索女性。这将是有价值的复制和确认这些发现在其他独立的研究，旨在最终找到隐藏在AAM变异背后的遗传机制。
Variation in age at menarche (AAM) is known to be substantially influenced by genetic factors, but the true causal genes remain largely unidentified. Because the increased amplitude of estrogen exposure of tissues initiates the onset of menarche, the genes involved in estrogen biosynthesis are natural candidate genes underlying AAM. Our study aimed to identify whether the CYP17 and CYP19, the two key genes involved in the biosynthesis of estrogen, are associated with AAM variation in 1048 females from 354 Caucasian nuclear families. We genotyped 38 SNPs and established the linkage disequilibrium blocks and haplotype structures that covered the full transcript length of those two genes. Family-based and population-based statistical analyses were used to test for associations with all of the single SNPs and haplotypes. Both methods consistently detected significant associations for five SNPs of CYP19 with AAM. Haplotype analyses corroborated our single-SNP results by showing that the haplotypes in block 1 were highly significant to AAM in population-based analyses. However, we could not find any association of CYP17 with AAM. Our study is the first to suggest the important effect of CYP19 on AAM variation in Caucasian females. It will be valuable to replicate and confirm these findings in other independent studies, aiming at eventually finding the hidden genetic mechanisms underlying the variation in AAM.