FMR1重复序列长度与卵巢功能障碍的关联

Association of FMR1 repeat size with ovarian dysfunction.

作者信息

Sullivan A K, Marcus M, Epstein M P, Allen E G, Anido A E, Paquin J J, Yadav-Shah M, Sherman S L

机构信息

Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

出版信息

Hum Reprod. 2005 Feb;20(2):402-12. doi: 10.1093/humrep/deh635. Epub 2004 Dec 17.

DOI:10.1093/humrep/deh635

PMID:15608041

Abstract

BACKGROUND

Women who carry the FMR1 premutation allele have a significantly increased risk for ovarian dysfunction. We hypothesize that molecular characteristics of the FMR1 gene may explain this increased risk.

METHODS

Thus, we examined the effect of FMR1 CGG repeat size and related factors on measures of ovarian dysfunction using data from 507 women with a wide range of repeat sizes.

RESULTS AND CONCLUSIONS

We found a significant positive association of repeat size with ovarian dysfunction, but have preliminary evidence that this relationship is non-linear. We suggest that FMR1 repeat size in the lower range (<80 repeats) contributes to the variation in age at menopause; thus, FMR1 could be considered a quantitative trait locus. More importantly, when repeat size exceeds this threshold, the increase in risk for ovarian dysfunction is clinically significant. Intriguingly, this risk appears to plateau, or perhaps decrease, among women with very high repeats (> or =100 repeats).

摘要

背景

携带FMR1前突变等位基因的女性卵巢功能障碍风险显著增加。我们推测FMR1基因的分子特征可能解释了这种风险增加的原因。

方法

因此，我们使用来自507名具有广泛重复长度的女性的数据，研究了FMR1 CGG重复长度及相关因素对卵巢功能障碍指标的影响。

结果与结论

我们发现重复长度与卵巢功能障碍之间存在显著正相关，但有初步证据表明这种关系是非线性的。我们认为，较低范围（<80次重复）的FMR1重复长度导致绝经年龄的差异；因此，FMR1可被视为一个数量性状位点。更重要的是，当重复长度超过这个阈值时，卵巢功能障碍风险的增加具有临床意义。有趣的是，在重复长度非常高（≥100次重复）的女性中，这种风险似乎趋于平稳，甚至可能降低。