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

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

Association analysis between <i>HIF2A</i> tSNPs and levels of high altitude among native Tibetans.

<p>Abbreviations: Additive, additive model; Dominant, dominant model.</p><p><i>P</i>-values except the noted ones are calculated from χ² test.</p><p>^<b>a</b><i>P</i>-values are calculated from Fisher exact test.</p><p>^<b>b</b> Bold type denotes <i>P</i><0.05.</p><p>Association analysis between <i>HIF2A</i> tSNPs and levels of high altitude among native Tibetans.</p

Clinical characteristics of the studied groups.

<p>Abbreviations: BMI, body mass index; RBC, red blood cell count, RBC; HB, hemoglobin; HCT, hematocrit; LVEF, left ventricular ejection fraction.</p><p>^<b>a</b> Data are means ± SD.</p><p>Clinical characteristics of the studied groups.</p

Correlation of allele frequencies of <i>HIF2A</i> variants in Tibetans and level of high altitude.

<p>solid circle, rs56721780-C; solid diamond, rs6756667-A; solid square, rs7589621-G; solid triangle, rs1868092-A</p

Allele Frequencies of the altitude-associated <i>HIF2A</i> tSNPs between populations.

<p>Abbreviations: TBT, Tibetan in Tibet; TBQ, Tibetan in Qinghai; CHB, Chinese Han in Beijing. Japanese in Tokyo, Japan.</p><p>^<b>a</b> From 1000 GENOMES, phase 1.</p><p>^<b>b</b> From Xu <i>et al</i>.2011.</p><p>^<b>c</b> From Simonson <i>et al</i>.2010.</p><p>^<b>d</b> No data.</p><p>Allele Frequencies of the altitude-associated <i>HIF2A</i> tSNPs between populations.</p

Association analysis between <i>HIF1A</i> tSNPs and levels of high altitude among native Tibetans.

<p>Abbreviations: Additive, additive model; Dominant, dominant model.</p><p><i>P</i>-values except the noted ones are calculated from χ² test.</p><p>^<b>a</b><i>P</i>-values are calculated from Fisher exact test.</p><p>^<b>b</b> Bold type denotes <i>P</i><0.05.</p><p>Association analysis between <i>HIF1A</i> tSNPs and levels of high altitude among native Tibetans.</p

Allelic frequencies of the markers with unadjusted <i>P</i><0.05.

<p>Note: Chr, Chromosome; A, Allele; OR, odds ratio;</p><p><i>p</i>, unadjusted <i>p</i> values,* <i>p</i><0.05;</p><p><i>p′</i>, adjusted <i>p</i> values, ** <i>p′</i><0.05.</p

Selection of candidate genes and SNPs.

<p>Selection of candidate genes and SNPs.</p