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G72(DAOA)假定风险单倍型对健康受试者认知功能的影响。

Effect of the G72 (DAOA) putative risk haplotype on cognitive functions in healthy subjects.

作者信息

Jansen Andreas, Krach Sören, Krug Axel, Markov Valentin, Eggermann Thomas, Zerres Klaus, Thimm Markus, Nöthen Markus M, Treutlein Jens, Rietschel Marcella, Kircher Tilo

机构信息

Section of BrainImaging, Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany.

出版信息

BMC Psychiatry. 2009 Sep 24;9:60. doi: 10.1186/1471-244X-9-60.

Abstract

BACKGROUND

In the last years, several susceptibility genes for psychiatric disorders have been identified, among others G72 (also named D-amino acid oxidase activator, DAOA). Typically, the high-risk variant of a vulnerability gene is associated with decreased cognitive functions already in healthy individuals. In a recent study however, a positive effect of the high-risk variant of G72 on verbal working memory was reported. In the present study, we therefore examined the relationship between G72 genotype status and a broad range of cognitive functions in 423 healthy individuals.

METHODS

The G72 carrier status was assessed by the two single nucleotide polymorphisms (SNPs) M23 and M24. Subjects were divided into three risk groups (low, intermediate and high risk).

RESULTS

G72 status influenced a number of cognitive functions, such as verbal working memory, attention, and, at a trend level, spatial working memory and executive functions. Interestingly, the high-risk allele carriers scored better than one or even both other groups.

CONCLUSION

Our data show that the putative high-risk haplotype (i.e. homozygote C/C-allele carriers in SNP M23 and homozygote T/T-allele carriers in SNP M24) is in healthy individuals not necessarily associated with worse performance in cognitive functions, but even with better performance in some domains. Further work is required to identify the mechanisms of G72 on brain functions.

摘要

背景

在过去几年中,已经确定了几种精神疾病的易感基因,其中包括G72(也称为D-氨基酸氧化酶激活剂,DAOA)。通常,易损基因的高风险变异体在健康个体中就与认知功能下降有关。然而,在最近的一项研究中,报告了G72高风险变异体对言语工作记忆有积极影响。因此,在本研究中,我们检查了423名健康个体中G72基因型状态与广泛认知功能之间的关系。

方法

通过两个单核苷酸多态性(SNP)M23和M24评估G72携带状态。受试者被分为三个风险组(低、中、高风险)。

结果

G72状态影响了许多认知功能,如言语工作记忆、注意力,以及在空间工作记忆和执行功能方面呈趋势性影响。有趣的是,高风险等位基因携带者的得分高于其他一个甚至两个组。

结论

我们的数据表明,假定的高风险单倍型(即SNP M23中的纯合子C/C等位基因携带者和SNP M24中的纯合子T/T等位基因携带者)在健康个体中不一定与认知功能较差相关,甚至在某些领域表现更好。需要进一步开展工作来确定G72对脑功能的作用机制。

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