Methylenetetrahydrofolate reductase C677T polymorphism and cognitive function in older women
Methylenetetrahydrofolate reductase C677T polymorphism and cognitive function in older women
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DOI：
10.1093/aje/kwm140
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发表时间：
2007-09-15
影响因子：
5
通讯作者：
Yaffe, Kristine
中科院分区：
文献类型：
--
作者：
Elkins, Jacob S.;Johnston, S. Claiborne;Yaffe, Kristine
同型半胱氨酸可能在认知能力下降中起因果作用。作者分析了5,10-亚甲基四氢叶酸还原酶（MTHFR） C677T基因型，该基因型与血浆同型半胱氨酸水平相关，研究对象为6653名骨质疏松性骨折研究参与者，这是一项基于社区的前瞻性队列研究，研究对象为美国四个州的老年妇女。在1986-1998年期间，作者评估了MTHFR C677T基因型的分布是否独立于潜在的混杂因素，以及TT基因型患者在标准认知测试中的基线表现是否较低，或表现出较大的纵向下降。尽管在整个队列中，种族与MTHFR基因型分布相关（p < 0.001），但在最大的种族同族亚组中，北欧和/或中欧血统的人（n = 5,668）中，所有测量的混杂因素似乎与MTHFR基因型无关（Kolmogorov-Smirnov p = 0.97）。在这个亚组中，TT基因型与数字符号替换测试（p = 0.034）和Trails B测试（p = 0.020）的较低分数相关，并且与迷你精神状态检查的修改版本的年度超额分数相关（p = 0.035）。虽然观察到的关联强度不大，但这些结果为同型半胱氨酸水平升高导致认知能力下降的理论提供了一些支持。
Homocysteine may play a causal role in cognitive decline. The authors analyzed the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T genotype, a correlate of plasma homocysteine levels, among 6,653 participants in the Study of Osteoporotic Fractures, a community-based, prospective cohort study of older women in four US states. During the years 1986-1998, the authors assessed whether the distribution of MTHFR C677T genotypes was independent of potential confounders and whether persons with the TT genotype had lower baseline performance or showed greater longitudinal declines on standard cognitive tests. Although ethnicity was associated with MTHFR genotype distribution within the entire cohort (p < 0.001), all measured confounders appeared independent of MTHFR genotype within the largest ethnically homogenous subgroup, persons of Northern and/or Central European ancestry (n = 5,668) (Kolmogorov-Smirnov p = 0.97). In this subgroup, the TT genotype was associated with lower scores on the Digit Symbol Substitution Test (p = 0.034) and the Trails B test (p = 0.020) and with a small excess annual decline on a modified version of the Mini-Mental State Examination (p = 0.035). Although the strength of the observed associations was modest, these results lend some support to the theory that an elevated homocysteine level contributes to cognitive decline.