Brief Article
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World J Gastroenterol. Oct 7, 2012; 18(37): 5276-5282
Published online Oct 7, 2012. doi: 10.3748/wjg.v18.i37.5276
Nur-related receptor 1 gene polymorphisms and alcohol dependence in Mexican Americans
Ya-Ming Wei, Yan-Lei Du, Yu-Qiang Nie, Yu-Yuan Li, Yu-Jui Yvonne Wan
Ya-Ming Wei, Department of Blood Transfusion, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, Guangdong Province, China
Yan-Lei Du, Yu-Qiang Nie, Yu-Yuan Li, Yu-Jui Yvonne Wan, Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, Guangdong Province, China
Yu-Jui Yvonne Wan, Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, KS 66160, United States
Author contributions: Wei YM, Wan YJ designed the study and assembled the data; Wei YM, Du YL drafted the article; and Nie YQ and Li YY critically reviewed the article.
Supported by NIH/NIAAA Grant RO1 AA 12081; and Centers of Biomedical Research Excellence Grant P20 RR021940
Correspondence to: Ya-Ming Wei, PhD, Department of Blood Transfusion, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, Guangdong Province, China. weiyaming@163.com
Telephone: +86-20-81045129 Fax: +86-20-81048643
Received: March 9, 2012
Revised: May 18, 2012
Accepted: May 26, 2012
Published online: October 7, 2012
Abstract

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.

Keywords: Nur-related receptor 1; Polymorphism; Alcohol dependence; Obesity; Smoking; Nuclear receptor