Polymorphisms of genes in neurotransmitter systems were associated with alcohol use disorders in a Tibetan population

PLoS One. 2013 Nov 27;8(11):e80206. doi: 10.1371/journal.pone.0080206. eCollection 2013.

Abstract

Studies of linkage and association in various ethnic populations have revealed many predisposing genes of multiple neurotransmitter systems for alcohol use disorders (AUD). However, evidence often is contradictory regarding the contribution of most candidate genes to the susceptibility of AUD. We, therefore, performed a case-control study to investigate the possible associations of genes selected from multiple neurotransmitter systems with AUD in a homogeneous Tibetan community population in China. AUD cases (N = 281) with an alcohol use disorder identification test (AUDIT) score ≥10, as well as healthy controls (N = 277) with an AUDIT score ≤5, were recruited. All participants were genotyped for 366 single nucleotide polymorphisms (SNPs) of 34 genes selected from those involved in neurotransmitter systems. Association analyses were performed using PLINK version 1.07 software. Allelic analyses before adjustment for multiple tests showed that 15 polymorphisms within seven genes were associated with AUD (p<0.05). After adjustment for the number of SNPs genotyped within each gene, only the association of a single marker (rs10044881) in HTR4 remained statistically significant. Haplotype analysis for two SNPs in HTR4 (rs17777298 and rs10044881) showed that the haplotype AG was significantly associated with the protective effect for AUD. In conclusion, the present study discovered that the HTR4 gene may play a marked role in the pathogenesis of AUD. In addition, this Tibetan population sample marginally replicated previous evidence regarding the associations of six genes in AUD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alcohol-Related Disorders / genetics*
  • Alleles
  • Asian People*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neurotransmitter Agents / genetics*
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Tibet

Substances

  • Neurotransmitter Agents

Grants and funding

Funded by a grant from the National Nature Science Foundation of China (grant No. 30870889) and a grant from the Department of Science and Technology, Sichuan, China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.