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儿茶酚-O-甲基转移酶基因Val158Met多态性与甲基苯丙胺依赖之间不存在关联。

Lack of association between the Val158Met catechol-O-methyltransferase gene polymorphism and methamphetamine dependence.

作者信息

Hosák Ladislav, Serý Omar, Beranek Martin, Alda Martin

机构信息

Department of Psychiatrics, Charles University, Hradec Králové, Czech Republic.

出版信息

Neuro Endocrinol Lett. 2011;32(4):469-74.

PMID:21876500
Abstract

OBJECTIVES

About 25,000 serious methamphetamine abusers live in the Czech Republic among the total population of 10 million. Dependence on methamphetamine is markedly related to the brain neurotransmitter dopamine, metabolised by catechol-O-methyltransferase enzyme. The main aim of the study was to ascertain whether the Val158Met catechol-O-methyltransferase gene polymorphism is associated with methamphetamine dependence in this Central European country.

METHODS

One hundred and twenty-three subjects dependent on methamphetamine (women N=44), parents of sixty-seven dependent individuals, and four hundred healthy controls (women N=250) were involved into the study. We performed a population-based as well as family-based genetic association studies.

RESULTS

We did not find any significant association between the Val158Met catechol-O-methyltransferase gene polymorphism and methamphetamine dependence using the population-based or family-based design (p=0.41-0.66; Chi-Square Test or UNPHASED program, Version 3.1.4, respectively). We found a trend toward a statistically significant difference between the Val allele carriers and Met/Met homozygotes in the frequence of psychotic symptoms induced by methamphetamine (more frequent in Val carriers; p=0.062; Chi-Square Test).

CONCLUSION

Further research involving haplotype analysis and other dopamine-related genetic polymorphisms in large populations is needed. More attention should also be paid to possible role of the Val158Met catechol-O-methyl-transferase gene polymorphism in individual clinical subtypes of dependence on methamphetamine involving e.g. psychotic features or violence.

摘要

目的

在捷克共和国1000万总人口中,约有25000名严重的甲基苯丙胺滥用者。对甲基苯丙胺的依赖与大脑神经递质多巴胺显著相关,多巴胺由儿茶酚-O-甲基转移酶代谢。本研究的主要目的是确定在这个中欧国家,Val158Met儿茶酚-O-甲基转移酶基因多态性是否与甲基苯丙胺依赖有关。

方法

123名甲基苯丙胺依赖者(女性44名)、67名依赖者的父母以及400名健康对照者(女性250名)参与了本研究。我们进行了基于人群和基于家系的基因关联研究。

结果

使用基于人群或基于家系的设计,我们未发现Val158Met儿茶酚-O-甲基转移酶基因多态性与甲基苯丙胺依赖之间存在任何显著关联(p = 0.41 - 0.66;分别为卡方检验或UNPHASED程序,版本3.1.4)。我们发现,在甲基苯丙胺诱发的精神病性症状频率方面,Val等位基因携带者与Met/Met纯合子之间存在统计学显著差异的趋势(Val携带者中更常见;p = 0.062;卡方检验)。

结论

需要在大量人群中进行进一步的研究,包括单倍型分析和其他与多巴胺相关的基因多态性。还应更多地关注Val158Met儿茶酚-O-甲基转移酶基因多态性在甲基苯丙胺依赖的个体临床亚型(如涉及精神病性特征或暴力)中的可能作用。

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