Population-specific functional variant of the TPH2 gene 2755C>A polymorphism contributes risk association to major depression and anxiety in Chinese peripartum women

Abstract

The rate-limiting enzyme of serotonin biosynthesis, tryptophan hydroxylase 2 (TPH2), is one of the most promising candidate genes for psychiatric disorders. Although evidence strongly suggests that the TPH2 is significant in the etiology of major depression and anxiety disorder, whether it also contributes to the etiology of peripartum major depression and anxiety disorder, a specific subtype influenced considerably by other environmental factors like hormones, is unclear. This study investigated the role of TPH2 in the etiology of peripartum major depression and anxiety disorder in a Han Chinese population in Taiwan. Six single nucleotide polymorphisms were selected from previously profiled genetic information of TPH2 in Han Chinese. A cohort of postpartum Chinese women that included 117 patients with major depression, anxiety disorder, or both and 83 healthy controls were genotyped with selected TPH2 markers. The TPH2 2755A allele was found only in women with peripartum major depression and anxiety disorder (p = 0.043) and exhibited a dominant gene action (p = 0.038) with an estimated disease risk of 1.73. Although the sample size is small, results from this study suggest that the TPH2 C2755A polymorphism may represent a population-specific risk factor for peripartum major depression and anxiety disorder, perhaps by interacting with hormones.

Tryptophan Hydroxylase 2 Gene Polymorphism in Anxiety and Depressive Disorder in Kashmiri Population

“…The TPH2 polymorphism genotype and allele frequency was found to be statically non-significant in case of anxiety disorder. Lin YM et al, and Youn JS reported association of anxiety with TPH2 polymorphism [6,19]. Similar findings have been reported earlier also [20,21].…”

“…It was found that patients with panic disorders had lower levels of circulating serotonin compared with controls in one study [3]. The gene of tryptophan hydroxylase, the rate limiting enzyme in the synthesis of serotonin, is widely recognized as a major candidate gene in many psychiatric disorders [4][5][6].Recently a new isoform of the enzyme (TPH2) has been identified.TPH2 is predominantly expressed in the brain stem, where the serotonergic raphe nuclei are located [4][5][6][7]. Therefore we planned to study the role of TPH2 gene in anxiety and depressive disorders in our Kashmiri population (India).…”

Genetic variants in the tryptophan hydroxylase 2 gene (TPH2) and depression during and after pregnancy

“…The TPH1 isoform is expressed in peripheral tissues, whereas TPH2 is brain and neuronspecific (Invernizzi, 2007;Walther et al, 2003). Two studies in Asian cohorts observed significant associations between single variants in the tryptophan hydroxylase (TPH) isoform 1 and 2 genes TPH1 and TPH2 and postpartum depression, in a caseecontrol design (Lin et al, 2009;Sun et al, 2004), but no association for polymorphisms in these genes was reported in larger Spanish study (Costas et al, 2010).…”

“…Given the evidence for the importance of tryptophan in peripartum depression (Kohl et al, 2005;Maes et al, 2002), this neuronal isoform of TPH is an important candidate gene for this disorder, currently with conflicting genetic association data from only two studies (Costas et al, 2010;Lin et al, 2009).…”

Administração prolongada do ácido 13-cis-retinóico (isotretinoína) em camundongos machos adolescentes: comportamentos emocionais e quantificação de transcritos de componentes do sistema serotoninérgico central.

“…Investigações em humanos encontraram correlações entre variações genéticas no gene da Tph2 com aumento da incidência de casos clínicos de depressão e suicídio (Zill et al, 2004a(Zill et al, , 2004b, com o risco de desenvolver quadro de ansiedade/depressão em mulheres em período peri-parto (Lin et al, 2009), bem como com a ocorrência de autismo (Coon et al, 2005).…”