TPH2 gene polymorphisms and major depression--a meta-analysis.
BACKGROUND
Tryptophan hydroxylase-2 (TPH2) is the rate-limiting enzyme in the synthetic pathway for brain serotonin and is considered key factor for maintaining normal serotonin transmission in the central neuron system (CNS). Gene-disease association studies have reported a relationship between TPH2 and major depressive disorder (MDD) in different populations, however subsequent studies have produced contradictory results.


OBJECTIVE
We performed a systematic overview and a meta-analysis with all available data up-to-date.


METHODS
We scrutinized PubMed, Embase, HuGNet and China National Knowledge Infrastructure (CNKI ) and last update was held on October 2011. We also searched the manuscripts and the supplementary documents of the published genome-wide association studies in the field. Effect sizes of independent loci that have been studied in more than 3 articles were synthesized using fixed and random effects models.


RESULTS
We found 27 eligible articles that studied a total of 74 single nucleotide polymorphisms (SNPs). Finally, 12 independent loci were included in the meta-analysis. The synthesis of the data shown that two SNPs (rs4570625 and rs17110747) were associated with MDD using fixed effects models. SNP rs4570625 had low heterogeneity and remained significant using the more conservative random effects calculations with a summary OR = 0.83 (95% CI: 0.73-0.96).


CONCLUSIONS
The current study identified a SNP (rs4570625) with strong epidemiological credibility; however more studies are required to provide robust evidence for other weak associations.
Department of Medical Psychology, Shandong University School of Medicine, Jinan, Shandong, China.
Jin
J
Gao
Zhenglun
Z
Pan
Zhian
Z
Jiao
Feng
F
Li
Guoqing
G
Zhao
Qianqian
Q
Wei
Fang
F
Pan
Evangelos
E
Evangelou
D003865:Major Depressive Disorder / Q000201:enzymology* / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D014365:Tryptophan Hydroxylase / Q000235:genetics*
C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase