Nur-related receptor 1 gene polymorphisms and alcohol dependence in Mexican Americans.
Nur-related receptor 1 gene polymorphisms and alcohol dependence in Mexican Americans.
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DOI：
10.3748/wjg.v18.i37.5276
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发表时间：
2012-10
影响因子：
4.3
通讯作者：
Yaming Wei;Yanlei Du;Y. Nie;Yu-yuan Li;Y. Wan
中科院分区：
文献类型：
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作者：
Yaming Wei;Yanlei Du;Y. Nie;Yu-yuan Li;Y. Wan
目的 探讨墨西哥裔美国人 nur 相关受体 1 (Nurr1) 多态性与酒精依赖发展的关系。方法 从 374 名酗酒者和 346 名不酗酒的墨西哥裔美国人中采集外周血样本；这两组的性别和年龄都匹配。提取样品 DNA，并通过聚合酶链式反应扩增基因组 DNA。用Sau96I消化-2922(C) 2-3聚合酶链反应产物，通过测序研究调节区中的1345(G/C)和-1198(C/G)等位基因以及外显子3中的Ex+132(G/T/A/C)和Ex+715(T/-)。结果 -2922(C) 2-3 的 C2/C2、C2/C3、C3/C3 基因型分布在非酒精组中分别为 34.4%、38.2% 和 27.5%，而在酒精组中分别为 23.3%、51.2% 和 25.4%（P = 0.001）。 -1198(C/G)的C/C、C/G、G/G基因型分布在非酒精组中分别为23.5%、46.1%和30.3%，而在酒精组中分别为13.9%、50.9%和35.3%(P = 0.007)。然而，-1345 (G/C)、Ex3+132(G/T/A/C) 和 Ex3+715(T/-) 等位基因在墨西哥裔美国人中不存在多态性，所有研究的人都分别具有这三个等位基因的 G/G、G/G 和 T/T 基因型。 -2922(C) 2-3 没有显示酒精和非酒精个体之间的等位基因水平差异，但 -1198 (C/G) 显示酒精 (39.3%) 和非酒精 (46.6%) 人群之间显着的等位基因频率差异 (P = 0.005)。排除肥胖个体，非肥胖酗酒者和非肥胖对照者之间的 -2922(C) 2-3 多态性（P = 0.000 和 P = 0.049）和 -1198 (C/G) 多态性（P = 0.008 和 P = 0.032）在基因型和等位基因水平上均存在显着差异。排除吸烟者，不吸烟酗酒者和不吸烟对照之间仅在-2922(C) 2-3 多态性的基因型水平上发现显着差异(P = 0.037)，但仅在-1198(C/G) 多态性的等位基因水平上发现显着差异(P = 0.034)。结论 Nurr1 调控区的多态性与酒精依赖的发病机制有关，Nurr1/多巴胺信号通路可能对墨西哥裔美国人的这种依赖发展很重要。
AIM To investigate the association of polymorphisms of nur-related receptor 1 (Nurr1) and development of alcohol dependence in Mexican Americans. METHODS Peripheral blood samples were collected from 374 alcoholic and 346 nonalcoholic Mexican Americans; these two groups were sex- and age-matched. Sample DNA was extracted and genomic DNA was amplified by polymerase chain reaction. The -2922(C) 2-3 polymerase chain reaction products were digested with Sau96I, alleles of 1345(G/C), and -1198(C/G) in the regulatory region as well as Ex+132 (G/T/A/C) and Ex+715(T/-) in exon 3 were studied by sequencing. RESULTS The C2/C2, C2/C3, C3/C3 genotype distribution of -2922(C) 2-3 was 34.4%, 38.2% and 27.5% in the nonalcoholic group compared to 23.3%, 51.2% and 25.4% in the alcoholic group (P = 0.001). The C/C, C/G, G/G genotype distribution of -1198(C/G) was 23.5%, 46.1% and 30.3% in the nonalcoholic group compared to 13.9%, 50.9% and 35.3% in the alcoholic group (P = 0.007). However, the -1345 (G/C), Ex3+132(G/T/A/C) and Ex3+715(T/-) alleles were not polymorphic in Mexican Americans, and all those studied had G/G, G/G and T/T genotype for these three alleles, respectively. The -2922(C) 2-3 did not show allele level difference between alcoholic and nonalcoholic individuals, but -1198 (C/G) showed a significant allele frequency difference between alcoholic (39.3%) and nonalcoholic (46.6%) populations (P = 0.005). Excluding obese individuals, significant differences were found at both genotypic and allelic levels for the -2922(C) 2-3 polymorphism (P = 0.000 and P = 0.049) and the -1198 (C/G) polymorphism (P = 0.008 and P = 0.032) between nonobese alcoholics and nonobese controls. Excluding smokers, a significant difference was found only at the genotypic level for the -2922(C) 2-3 polymorphism (P = 0.037) between nonsmoking alcoholics and nonsmoking controls, but only at the allelic level for the -1198(C/G) polymorphism (P = 0.034). CONCLUSION Polymorphisms in the regulatory region of Nurr1 are implicated in pathogenesis of alcohol dependence and the Nurr1/dopamine signaling pathway might be important for this dependence development in Mexican Americans.