Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, USA.
Neurology. 2013 Jan 1;80(1):92-9. doi: 10.1212/WNL.0b013e3182768910. Epub 2012 Nov 7.
To determine whether 4 genetic variants in the fat mass and obesity associated gene (FTO) identified in genome-wide association studies of diabetes and obesity are associated with cognitive change in midlife in the Atherosclerosis Risk in Communities (ARIC) Study.
ARIC is a prospective cohort study of the development of atherosclerosis in 15,792 individuals aged 45 to 64 years at baseline from 1986 to 1989. FTO is highly expressed in human fetal and adult brain, and a single nucleotide polymorphism in FTO has previously been associated with reduced brain volume in cognitively normal subjects. Since a relationship between brain atrophy and diminished cognitive function has been demonstrated in ARIC participants, general linear models were used to evaluate the association between 6-year change in scores on 3 neuropsychological tests and FTO genotype.
In a sample of 8,364 white and 2,083 African American men and women with no clinical history of stroke, significantly greater mean change in performance on the Delayed Word Recall Test was associated with 2 of 4 FTO single nucleotide polymorphisms examined (rs9939609, rs805136, rs17817449, and rs1421085) in whites but not in African Americans (p ≤ 0.002). The association of the FTO polymorphisms with cognitive change was independent of potential confounding clinical and demographic variables including age, gender, education, diabetes, hypertension, and body mass index.
Further studies will be needed to clarify the biological mechanisms and genetic pathways through which variants in FTO can increase susceptibility to decline in verbal memory detectable in middle-aged, community-dwelling adults.
确定在糖尿病和肥胖的全基因组关联研究中发现的脂肪量和肥胖相关基因（FTO）中的 4 个遗传变异是否与动脉粥样硬化风险社区（ARIC）研究中年中期的认知变化有关。
ARIC 是一项前瞻性队列研究，研究了 1986 年至 1989 年基线时年龄在 45 至 64 岁的 15792 名个体的动脉粥样硬化发展情况。FTO 在人类胎儿和成人脑中高度表达，FTO 中的单核苷酸多态性先前与认知正常受试者的脑容量减少有关。由于在 ARIC 参与者中已经证明了脑萎缩与认知功能下降之间的关系，因此使用一般线性模型来评估 3 项神经心理学测试得分的 6 年变化与 FTO 基因型之间的关系。
在一个没有中风临床病史的白人 8364 名和黑人 2083 名男性和女性样本中，延迟单词回忆测试的表现有明显更大的平均变化与所检查的 4 个 FTO 单核苷酸多态性中的 2 个相关（rs9939609、rs805136、rs17817449 和 rs1421085）在白人中，但不在黑人中（p≤0.002）。FTO 多态性与认知变化的关联独立于潜在的混杂临床和人口统计学变量，包括年龄、性别、教育、糖尿病、高血压和体重指数。
需要进一步研究来阐明 FTO 变异增加中年、社区居住成年人中可检测到的言语记忆下降易感性的生物学机制和遗传途径。
