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芬兰男性酗酒者单胺氧化酶A(MAOA)启动子多态性分析。

Analysis of monoamine oxidase A (MAOA) promoter polymorphism in Finnish male alcoholics.

作者信息

Saito Takuya, Lachman Herbert M, Diaz Libna, Hallikainen Tero, Kauhanen Jussi, Salonen Jukka T, Ryynänen Olli-Pekka, Karvonen Matti K, Syvälahti Erkka, Pohjalainen Tiina, Hietala Jarmo, Tiihonen Jari

机构信息

Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.

出版信息

Psychiatry Res. 2002 Mar 15;109(2):113-9. doi: 10.1016/s0165-1781(02)00013-6.

Abstract

Alterations in monoamine oxidase A (MAOA) expression and enzyme activity may be associated with alcoholism and impulsive behavior. Therefore, functional polymorphisms in the MAOA gene would be good candidates to consider in the interindividual differences that exist in the susceptibility to alcoholism. One variant that has been considered as a candidate in alcoholism is a repeat polymorphism in the MAOA gene promoter. We analyzed a cohort of Finnish males with either type 1 or type 2 alcoholism, as well as controls, for differences in the distribution of MAOA promoter alleles. Based on other studies, we postulated that type 2 alcoholism, which is associated with antisocial behavior, but not type 1 alcoholism, would be correlated with the inheritance of the low promoter activity allele. However, we failed to find a difference in allele distribution in type 1 and type 2 alcoholics. In addition, there was no difference in the allele distribution when each group of alcoholics was compared with controls. However, when both groups of alcoholics were pooled and compared with controls, the difference in allele distribution reached a trend towards significance. Our results suggest a minimal association between the MAOA low activity promoter alleles and alcoholism, regardless of the presence or absence of antisocial behavior. Interestingly, approximately 3% of type 2 alcoholics were found to be heterozygous for the MAOA promoter polymorphism. Since MAOA is X-linked, the heterozygotes are probable cases of Klinefelter's syndrome (47,XXY) suggesting that X-chromosome aneuploidy may increase the risk for developing type 2 alcoholism.

摘要

单胺氧化酶A(MAOA)表达和酶活性的改变可能与酒精中毒和冲动行为有关。因此,MAOA基因中的功能性多态性是考虑酒精中毒易感性个体差异时的良好候选因素。MAOA基因启动子中的重复多态性被认为是酒精中毒的一个候选变异。我们分析了一组患有1型或2型酒精中毒的芬兰男性以及对照组,以研究MAOA启动子等位基因分布的差异。基于其他研究,我们推测与反社会行为相关的2型酒精中毒而非1型酒精中毒,会与低启动子活性等位基因的遗传相关。然而,我们未能在1型和2型酒精中毒者中发现等位基因分布的差异。此外,将每组酒精中毒者与对照组进行比较时,等位基因分布也没有差异。但是,当将两组酒精中毒者合并并与对照组比较时,等位基因分布的差异达到了显著趋势。我们的结果表明,无论是否存在反社会行为,MAOA低活性启动子等位基因与酒精中毒之间的关联极小。有趣的是,发现约3%的2型酒精中毒者为MAOA启动子多态性的杂合子。由于MAOA是X连锁的,杂合子可能是克兰费尔特综合征(47,XXY)的病例,这表明X染色体非整倍性可能会增加患2型酒精中毒的风险。

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