Association between the TPH1 A218C polymorphism and risk of mood disorders and alcohol dependence: evidence from the current studies

Background: Several studies have assessed the association between genetic polymorphisms of tryptophan hydroxylase (TPH1) and risk of mood disorders and alcohol dependence, with controversial results. Our aim was to assess the association of TPH1 A218C polymorphism (rs1800532) with mood disorders, including major depressive disorder and bipolar disorder, and alcohol dependence by using meta-analysis.

Methods: Data were collected from the related literatures published until November 25, 2010 from MEDLINE, EMBASE and ISI Web of Science databases, and meta-analysis stratified by ethnicity was performed in either fixed or random effect model as appropriate by using Stata Statistical Package (version 10.0).

Results: Twenty-seven individual studies were included in the current study, among which, there were 9 studies for bipolar disorder, with 1951 cases and 2161 controls, 14 studies for major depressive disorder, with 2340 cases and 3204 controls, and 4 studies for alcohol dependence, with 601 cases and 711 controls. We found that in Caucasian population, the TPH1 218AA genotype was significantly associated with increased bipolar disorder risk (recessive comparison: OR, 1.42; Bonferroni-adjusted P=0.006; homozygote comparison: OR, 1.63; Bonferroni-adjusted P=0.072), and elevated alcohol dependence risk (recessive comparison: OR, 1.83; Bonferroni-adjusted P=0.012), while the association was not significant in Asian population. Moreover, the A218C polymorphism did not appear to have any effect on major depressive disorder risk either in Caucasians or in Asians.

Conclusion: The TPH1 A218C polymorphism is a potential biomarker for bipolar disorder and alcohol dependence risk in Caucasian population.