反社会型酒精中毒与5-羟色胺5-HT1B受体基因在两个群体中的连锁关系。

Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations.

作者信息

Lappalainen J, Long J C, Eggert M, Ozaki N, Robin R W, Brown G L, Naukkarinen H, Virkkunen M, Linnoila M, Goldman D

机构信息

Section of Population Genetics and Linkage, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20852, USA.

出版信息

Arch Gen Psychiatry. 1998 Nov;55(11):989-94. doi: 10.1001/archpsyc.55.11.989.

DOI:10.1001/archpsyc.55.11.989

PMID:9819067

Abstract

BACKGROUND

In mice, quantitative trait locus studies and behavioral evaluation of animals deleted for 5-HT1B have implicated this serotonin autoreceptor in alcohol consumption and aggressive behavior. We therefore investigated whether the 5-HT1B gene (HTR1B) is linked to alcoholism with aggressive and impulsive behavior in the human, as represented by 2 psychiatric diagnoses: antisocial personality disorder and intermittent explosive disorder comorbid with alcoholism.

METHODS

Linkage was first tested in 640 Finnish subjects, including 166 alcoholic criminal offenders, 261 relatives, and 213 healthy controls. This was followed by a study in a large multigenerational family derived from a Southwestern American Indian tribe (n=418) with a high rate of alcoholism. All subjects were psychiatrically interviewed, blind-rated for psychiatric diagnoses, and typed for a HTR1B G861C polymorphism and for a closely linked short-tandem repeat locus, D6S284. Linkage was evaluated in sib pairs, and by using an association approach in which pedigree randomization corrects for nonindependence of observations on related subjects.

RESULTS

In Finnish sib pairs, antisocial alcoholism showed significant evidence of linkage to HTR1B G861C (P=.04) and weak evidence with D6S284 (P=.06). By association analysis, the 183 Finnish antisocial alcoholics had a significantly higher HTR1B-861C allele frequency than the other 457 Finns we studied (P=.005). In the Southwestern American Indian tribe, significant sib pair linkage of antisocial alcoholism to HTR1B G861C (P=.01) was again observed, and there was also significant linkage to D6S284 (P=.01).

CONCLUSION

These results suggest that a locus predisposing to antisocial alcoholism may be linked to HTR1B at 6q13-15.

摘要

背景

在小鼠中，对5-HT1B基因缺失的动物进行数量性状基因座研究和行为评估表明，这种5-羟色胺自身受体与酒精消耗及攻击行为有关。因此，我们研究了5-HT1B基因（HTR1B）是否与人类的酒精中毒以及伴有攻击和冲动行为相关，这些行为表现为两种精神疾病诊断：反社会人格障碍以及与酒精中毒共病的间歇性爆发障碍。

方法

首先在640名芬兰受试者中进行连锁分析，其中包括166名酗酒的罪犯、261名亲属以及213名健康对照者。随后，对一个来自美国西南部印第安部落的大型多代家族（n = 418）进行研究，该家族酗酒率很高。所有受试者均接受了精神病学访谈，由不知情的人员对其进行精神疾病诊断评分，并对HTR1B G861C多态性以及紧密连锁的短串联重复序列位点D6S284进行分型。在同胞对中评估连锁情况，并采用关联分析方法，其中谱系随机化校正了相关受试者观察值的非独立性。

结果

在芬兰同胞对中，反社会型酒精中毒显示出与HTR1B G861C存在显著的连锁证据（P = 0.04），与D6S284存在较弱的连锁证据（P = 0.06）。通过关联分析，183名芬兰反社会型酗酒者的HTR1B - 861C等位基因频率显著高于我们研究的其他457名芬兰人（P = 0.005）。在美国西南部印第安部落中，再次观察到反社会型酒精中毒与HTR1B G861C存在显著的同胞对连锁（P = 0.01），并且与D6S284也存在显著连锁（P = 0.01）。