Examination of the effect of the polymorphic CGG repeat in the FMR1 gene on cognitive performance
Examination of the effect of the polymorphic CGG repeat in the FMR1 gene on cognitive performance
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DOI：
10.1007/s10519-005-2792-4
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发表时间：
2005-07-01
影响因子：
2.6
通讯作者：
Letz, R
中科院分区：
文献类型：
--
作者：
Allen, EG;Sherman, S;Letz, R
位于FMR 1基因5 ′非翻译区的CGG重复序列在亲子传递过程中重复序列的大小和稳定性方面具有多态性。当扩展到超过200个重复时，该基因被高度甲基化并沉默，导致脆性X综合征（FXS）。最近，具有大的未甲基化重复序列（前突变）的等位基因与卵巢功能衰竭和迟发性震颤/共济失调综合征相关，这些症状与FXS无关。为了进一步研究高重复等位基因的表型后果，我们分析了韦氏成人智力量表-III（WAIS-III）的措施，66名男性和217名女性具有广泛的重复大小。仅在女性中，我们发现FMR 1重复序列大小和转录水平显著解释了言语智商汇总测量中约4%的方差，这表明这种多态性是影响认知表现变化的众多因素之一。由于重复次数的增加与绝经年龄的降低之间存在着良好的相关性，我们还研究了生殖阶段和激素替代疗法（HRT）的使用作为模型语言智商（VIQ）的协变量。我们发现，它解释了另外5%的变异VIQ，但没有与FMR 1重复和转录水平的相互作用。
A CGG repeat sequence located in the 5' untranslated region of the FMR1 gene is polymorphic with respect to size and stability of the repeat during parent-offspring transmission. When expanded to over 200 repeats, the gene is hypermethylated and silenced, leading to fragile X syndrome (FXS). Recently, alleles with large unmethylated repeat tracts (premutations) have been associated with ovarian failure and a late-onset tremor/ataxia syndrome, symptoms unrelated to FXS. To further investigate the phenotype consequence of high repeat alleles, we have analyzed Wechsler adult intelligence scales-III (WAIS-III) measures on 66 males and 217 females with a wide range of repeat sizes. Among females only, we found that FMR1 repeat size and transcript level significantly explained approximately 4% of the variance in the Verbal IQ summary measure, suggesting that this polymorphism is one of many factors that influence variation in cognitive performance. Because of the well established association of increasing repeat size with decreasing age at menopause, we also investigated the reproductive stage and use of hormone replacement therapy (HRT) as a covariate to model verbal intelligence quotient (VIQ). We found that it explained an additional 5% of the variance in VIQ, but did not interact with FMR1 repeat and transcript level.