ADH1B*1, ADH1C*2, DRD2 (-141C Ins), and 5-HTTLPR are associated with alcoholism in Mexican American men living in Los Angeles

Background: The aim of the present study was to use a candidate gene approach to identify the genetic risk factors for alcoholism in Mexican Americans residing in the Los Angeles area. The genes selected include alcohol metabolizing genes and neurotransmitter genes, which have been shown in the literature to be associated with alcoholism in other ethnic groups. Methods: Thirteen allelic variants from seven genes were evaluated for their role in alcoholism using alcoholic (n = 200) and nonalcoholic (n = 251) Mexican Americans. Those polymorphic sites include alcohol dehydrogenase (ADH1B, ADH1C), aldehyde dehydrogenase (ALDH2), cytochrome P-450 2E1 (CYP2E1) TaqI, DraI, RsaI, dopamine D₂ receptor (DRD2) TaqI A, B, intron 6, exon 7, -141C Ins/Del, serotonin transporter (5-HTTLPR), and GABA_A receptor β3 subunit (GABRβ3). Results: The results demonstrate that Mexican Americans have extremely low allele frequency for both ALDH2*2 and ADH1B*2 and a relatively high frequency ADH1C*2 and CYP2E1 c2 alleles. ADH1B*1, ADH1C*2, DRD2 (- 141C Ins), and 5-HTTLPR were associated with alcoholism in Mexican Americans (p < 0.05). DRD2 Ins was associated with alcoholism in those alcoholics who carried the ADH1B*2 or ADH1C*1 protective alleles (p = 0.032 in genotype level and p = 0.015 in allele level). DRD2 TaqI A and B alleles were associated with early age of onset for drinking (p = 0.016 for TaqI A1 and p = 0.049 for TaqI B1 allele). Conclusions: Together, the data reveal unique genetic patterns in Mexican Americans that may be in part responsible for the heightened risk for alcoholism and alcohol-associated health problems in this population.