The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders.
The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders.
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DOI：
10.1001/jama.1991.03470130073032
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发表时间：
1991-10
期刊：
影响因子：
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通讯作者：
D. Comings;Comings Bg;D. Muhleman;G. Dietz;B. Shahbahrami;David E Tast;E. Knell;P. Kocsis;R. Baumgarten;Kovacs Bw
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文献类型：
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作者：
D. Comings;Comings Bg;D. Muhleman;G. Dietz;B. Shahbahrami;David E Tast;E. Knell;P. Kocsis;R. Baumgarten;Kovacs Bw
目的——先前报道多巴胺 D2 受体 (DRD2) 基因 Taq I 多态性的 A1 等位基因出现在 69% 的酗酒者中，而对照组的这一比例为 20%。其他研究报告称，酗酒者与对照组的 A1 等位基因患病率没有显着差异，也没有证据表明 DRD2 基因与酗酒有关。我们假设这些看似矛盾的结果可能是因为 A1 等位基因患病率的增加可能不是酗酒所特有的。因此，我们检查了经常与酗酒相关的其他疾病或那些被认为涉及多巴胺能神经传递缺陷的疾病。设计——案例比较研究。为了尽量减少种族差异对基因频率的影响，该研究仅限于非西班牙裔白人。背景——门诊和住院患者。结果——在所有已知对照 (n = 314) 中，77 个 (24.5%) 携带 A1 等位基因。在 69 名已知非酗酒者的对照中，10 名（14.5%）携带 A1 等位基因。在抽动秽语综合征（44.9%，n = 147）、注意力缺陷多动障碍（46.2%，n = 104）、自闭症（54.5%，n = 33）、酗酒（42.3%，n = 104）和创伤后应激障碍（45.7%，n = 35）患者中，A1等位基因的患病率显着增加。经过多重比较校正后（要求 P 小于 0.0009 才具有显着性），除创伤后应激障碍外，所有结果均保持显着。在抑郁症、惊恐发作、帕金森病或肥胖症患者中，A1 等位基因的患病率并未显着增加。 A1 等位基因在吸毒成瘾和精神分裂症中的患病率仅在与非酗酒者的对照组相比时才显着，并且未对多重比较进行校正。结论——这些结果表明 DRD2 基因的 A1 等位基因与许多行为障碍相关，在这些行为障碍中，它可能充当修饰基因而不是主要病因。
OBJECTIVE --The A1 allele of the Taq I polymorphism of the dopamine D2 receptor (DRD2) gene has been earlier reported to occur in 69% of alcoholics, compared with 20% of controls. Other research has reported no significant difference in the prevalence of the A1 allele in alcoholics vs controls and no evidence that the DRD2 gene was linked to alcoholism. We hypothesized that these seemingly conflicting results might be because increases in the prevalence of the A1 allele may not be specific to alcoholism. Thus, we examined other disorders frequently associated with alcoholism or those believed to involve defects in dopaminergic neurotransmission. DESIGN --Case comparison study. To minimize the effect of racial differences in gene frequencies, the study was restricted to non-Hispanic whites. SETTING --Ambulatory and hospitalized patients. RESULTS --Among all known controls (n = 314), 77 (24.5%) carried the A1 allele. Of the 69 controls known not to be alcoholics, 10 (14.5%) carried the A1 allele. The prevalence of the A1 allele was significantly increased in patients with Tourette's syndrome (44.9%, n = 147), attention deficit hyperactivity disorder (46.2%, n = 104), autism (54.5%, n = 33), alcoholism (42.3%, n = 104), and posttraumatic stress disorder (45.7%, n = 35). After correction for multiple comparisons (requiring P less than .0009 for significance), all remained significant except posttraumatic stress disorder. The prevalence of the A1 allele was not significantly increased in patients with depression, panic attacks, Parkinson's disease, or obesity. The prevalence of the A1 allele in drug addiction and schizophrenia was only significant when compared with that of controls who were not alcoholics, and no correction was made for multiple comparisons. CONCLUSION --These results suggest the A1 allele of the DRD2 gene is associated with a number of behavior disorders in which it may act as a modifying gene rather than as the primary etiological agent.