Nur-related receptor 1 gene polymorphisms and alcohol dependence in Mexican Americans

• Published in: World journal of gastroenterology : WJG 2012-10, Vol.18 (37), p.5276-5282
• Main Authors: Wei, Ya-Ming, Du, Yan-Lei, Nie, Yu-Qiang, Li, Yu-Yuan, Wan, Yu-Jui
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alcoholism - ethnology; Alcoholism - genetics; Alleles; Brief; Cohort Studies; Dopamine - metabolism; Exons; Female; Genetic Predisposition to Disease; Genotype; Humans; Male; Mexican Americans; Middle Aged; Nuclear Receptor Subfamily 4, Group A, Member 2 - genetics; Polymerase Chain Reaction - methods; Polymorphism, Genetic; Signal Transduction; Smoking; 受体; 基因水平; 基因组DNA; 墨西哥; 等位基因多态性; 美国人; 聚合酶链反应; 酒精性
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v18.i37.5276

AIM： To investigate the association of polymorphisms of nur-related receptor 1 （Nurrl） and development of alcohol dependence in Mexican Americans. METHODS： Peripheral blood samples were collected from 374 alcoholic and 346 nonalcoholic Mexican Amer- icans; 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 distribu- tion 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/6） 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 Mex- ican 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 be- tween 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） polymor- phism （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 con- trols, but only at the allelic level for the -1198（C/G） polymorphism （P = 0.034）. CONCLUSION： Polymorphisms in the regulatory region of Nurrl are implicated in pathogenesis of alcohol de- pendence and the Nurrl/dopamine signaling pathway might be important for this dependence development in Mexican Americans.