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老年女性的认知表现:多巴胺β-羟化酶基因5'侧翼19bp插入/缺失多态性、教育水平、身体脂肪测量、血清甘油三酯、饮酒量及年龄的意义。

Cognitive performance in elderly women: significance of the 19bp insertion/deletion polymorphism in the 5' flank of the dopamine beta-hydroxylase gene, educational level, body fat measures, serum triglyceride, alcohol consumption and age.

作者信息

Togsverd Mads, Werge Thomas M, Tankó Laszlo B, Bagger Yu Z, Qin George G, Hansen Thomas, Christiansen Claus, Rasmussen Henrik B

机构信息

Research Institute of Biological Psychiatry, H:S Sct. Hans Hospital, Roskilde, Copenhagen University, Denmark.

出版信息

Int J Geriatr Psychiatry. 2007 Sep;22(9):883-9. doi: 10.1002/gps.1756.

Abstract

BACKGROUND

Genetic and environmental factors influence cognitive aging. The gene encoding dopamine beta-hydroxylase (DBH) could be one such factor since this hydroxylase converts dopamine to norepinephrine both of which are involved in cognition regulation.

OBJECTIVE

To assess the effect of the 19bp insertion/deletion polymorphism in the 5' flank of the DBH gene on cognitive performance in elderly women relative to other factors of cognitive aging.

METHODS

We examined a cross-sectional sample of 1371 postmenopausal women. Cognitive abilities were assessed by the 6-item orientation-memory-concentration test. The 19bp insertion/deletion polymorphism of the DBH gene was genotyped and apolipoprotein E (APOE) epsilon4 allele status was determined. In addition blood pressure, body fat mass and blood lipids were measured. Information was also obtained by personal interviews. Data were analyzed by regression analysis.

RESULTS

Cognition was univariately associated with DBH genotype (p = 0.04). A univariate association of borderline significance was observed for APOE epsilon4 allele status (p = 0.07). Exclusion of women with severe cognition impairment did not alter the strength of the association with the DBH gene polymorphism markedly (p = 0.06) but obliterated the weak association between APOE epsilon4 allele status and cognition. The association of the DBH gene polymorphism with cognition persisted after adjustment for other variables (p = 0.03).

CONCLUSIONS

The 19bp insertion/deletion polymorphism of the DBH gene influences cognition in elderly women and might have a stronger effect than APOE epsilon4 allele status on mild cognitive impairment. Both genetic polymorphisms had a significantly smaller impact on cognition than age, education, alcohol consumption and body fat measures.

摘要

背景

遗传和环境因素影响认知衰老。编码多巴胺β-羟化酶(DBH)的基因可能是其中一个因素,因为这种羟化酶将多巴胺转化为去甲肾上腺素,二者均参与认知调节。

目的

评估DBH基因5'侧翼19bp插入/缺失多态性对老年女性认知表现的影响,并与其他认知衰老因素进行比较。

方法

我们对1371名绝经后女性进行了横断面研究。通过6项定向-记忆-注意力测试评估认知能力。对DBH基因的19bp插入/缺失多态性进行基因分型,并确定载脂蛋白E(APOE)ε4等位基因状态。此外,测量血压、体脂量和血脂。还通过个人访谈获取信息。采用回归分析对数据进行分析。

结果

认知与DBH基因型单因素相关(p = 0.04)。APOE ε4等位基因状态存在边缘显著性单因素关联(p = 0.07)。排除严重认知障碍女性后,与DBH基因多态性的关联强度未明显改变(p = 0.06),但消除了APOE ε4等位基因状态与认知之间的微弱关联。在对其他变量进行调整后,DBH基因多态性与认知的关联仍然存在(p = 0.03)。

结论

DBH基因的19bp插入/缺失多态性影响老年女性的认知,并且对轻度认知障碍的影响可能比APOE ε4等位基因状态更强。两种基因多态性对认知的影响均显著小于年龄、教育程度、饮酒量和体脂测量结果。

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