CYP2D6*4基因多态性与老年人抑郁或焦虑之间的关联。

Association between the CYP2D6*4 polymorphism and depression or anxiety in the elderly.

作者信息

Bijl Monique J, Luijendijk Hendrika J, van den Berg Julia F, Visser Loes E, van Schaik Ron H N, Hofman Albert, Vulto Arnold G, van Gelder Teun, Tiemeier Henning, Stricker Bruno H Ch

机构信息

Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.

出版信息

Pharmacogenomics. 2009 Apr;10(4):541-7. doi: 10.2217/pgs.09.9.

DOI:10.2217/pgs.09.9

PMID:19374513

Abstract

INTRODUCTION

5-methoxytryptamine (5-MT), a precursor of serotonin, is considered to be an endogenous substrate of cytochrome P450 2D6 (CYP2D6). Homozygous carriers of the variant allele CYP2D6*4 lack CYP2D6 enzyme activity. Relative to extensive metabolizers, these poor metabolizers may have lower baseline serotonin concentrations in various brain regions, and may be more prone to depression or anxiety.

AIM

To test whether the CYP2D6*4/*4 genotype is associated with a predisposition to depression or anxiety disorders in the elderly.

MATERIALS & METHODS: We conducted a cross-sectional study within the Rotterdam Study, a population-based cohort study, among persons aged 55 years or older, who were screened for depression and anxiety disorders at two consecutive examination rounds. Logistic regression was used to analyze the association between the CYP2D6*4 polymorphism and the risk of depression or anxiety disorders.

RESULTS

The risk of major depression in CYP2D6*4/*4 was not significantly different from extensive metabolizers (OR = 0.85; 95% CI: 0.36-2.00; p = 0.72). Neither did we find an association between CYP2D6 genotype and minor depression (OR = 1.56; 95% CI: 0.69-3.52; p = 0.28). No increased risk of anxiety disorders was found (OR = 1.19; 95% CI: 0.68-2.09; p = 0.55).

CONCLUSION

Variation in the CYP2D6 gene is not related to a predisposition to depression or anxiety disorders in the elderly.

摘要

引言

5-甲氧基色胺（5-MT）是血清素的前体，被认为是细胞色素P450 2D6（CYP2D6）的内源性底物。变异等位基因CYP2D6*4的纯合携带者缺乏CYP2D6酶活性。相对于广泛代谢者，这些慢代谢者在各个脑区的血清素基线浓度可能较低，并且可能更容易患抑郁症或焦虑症。

目的

测试CYP2D6*4/*4基因型是否与老年人患抑郁症或焦虑症的易感性相关。

材料与方法

我们在鹿特丹研究（一项基于人群的队列研究）中，对55岁及以上的人群进行了横断面研究，这些人在连续两轮检查中接受了抑郁症和焦虑症筛查。采用逻辑回归分析CYP2D6*4多态性与抑郁症或焦虑症风险之间的关联。

结果

CYP2D6*4/*4基因型患者患重度抑郁症的风险与广泛代谢者无显著差异（比值比=0.85；95%置信区间：0.36-2.00；p=0.72）。我们也未发现CYP2D6基因型与轻度抑郁症之间存在关联（比值比=1.56；95%置信区间：0.69-3.52；p=0.28）。未发现焦虑症风险增加（比值比=1.19；95%置信区间：0.68-2.09；p=0.55）。