A genotype of exceptional longevity is associated with preservation of cognitive function
A genotype of exceptional longevity is associated with preservation of cognitive function
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DOI：
10.1212/01.wnl.0000249116.50854.65
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发表时间：
2006-12-26
期刊：
影响因子：
9.9
通讯作者：
Lipton, R. B.
中科院分区：
文献类型：
--
作者：
Barzilai, N.;Atzmon, G.;Lipton, R. B.
目的：测试胆固醇酯转运蛋白（CETP）基因型（I405 V的VV纯合性）除了与长寿相关外，是否与认知功能的保留相关。研究方法：我们使用简易精神状态检查（MMSE）研究了长寿的德系犹太人（n = 158;年龄99.2 ± 0.3岁）CETP VV基因型和脂蛋白表型的关系。为了证实CETP在年轻人群中的作用，我们研究了爱因斯坦衰老研究（EAS）中CETP VV和认知障碍之间的关联。结果如下：MMSE > 25的受试者有CETP VV基因型的可能性是其两倍（29%对14%，p = 0.02），而VV基因型的受试者更有可能（61%对30%，p = 0.02）有MMSE > 25。VV基因型受试者的CETP水平较低（1.73 +/-0.11vs2.12 +/-0.10 μ g/ mL，p = 0.01），高密度脂蛋白（HDL）水平较高（p = 0.02），脂蛋白颗粒较大（p = 0.03）.在EAS队列中，VV基因型增加约5倍（21%对4%，p = 0.02），高密度脂蛋白水平较高，脂蛋白颗粒大小较大，与痴呆较少和记忆力改善相关。结论：使用两个独立的队列，我们暗示长寿CETP基因作为年龄相关的认知功能的调节剂。特定的CETP基因型与较低的CETP水平和有利的脂蛋白谱相关。还没有确定是否该基因的调节防止年龄相关的衰退或AD。
Objective: To test whether cholesterol ester transfer protein (CETP) genotype (VV homozygosity for I405V) is associated with preservation of cognitive function in addition to its association with exceptional longevity. Methods: We studied Ashkenazi Jews with exceptional longevity (n = 158; age 99.2 +/- 0.3 years) for the associations of CETP VV genotype and lipoprotein phenotype, using the Mini- Mental State Examination (MMSE). To confirm the role of CETP in a younger cohort, we studied subjects from the Einstein Aging Study (EAS) for associations between CETP VV and cognitive impairment. Results: Subjects with MMSE > 25 were twice as likely to have the CETP VV genotype (29% vs 14%, p = 0.02), and those with the VV genotype were more likely (61% vs 30%, p = 0.02) to have MMSE > 25. Subjects with the VV genotype had lower levels of CETP (1.73 +/- 0.11 vs 2.12 +/- 0.10 mu g/ mL, p = 0.01), higher high- density lipoprotein (HDL) levels (p = 0.02), and larger lipoprotein particles (p = 0.03). In the EAS cohort, an approximately fivefold increase in the VV genotype (21% vs 4%, p = 0.02), higher HDL levels, and larger lipoprotein particle sizes were associated with less dementia and improved memory. Conclusions: Using two independent cohorts, we implicate the longevity CETP gene as a modulator of age- related cognitive function. A specific CETP genotype is associated with lower CETP levels and a favorable lipoprotein profile. It has not been determined whether modulation of this gene prevents age- related decline or AD.