Associations between polymorphic variants of the tryptophan hydroxylase 2 gene and obsessive-compulsive disorder

Abstract

OBJECTIVE: A substantial body of evidence suggests that obsessive-compulsive disorder has a genetic component, and substantial candidate genes for the disorder have been investigated through association analyses. A particular emphasis has been placed on genes related to the serotonergic system, which is likely to play an important role in the pathogenesis of obsessive-compulsive disorder. The gene for tryptophan hydroxylase 2, which is a rate limiting enzyme in serotonin synthesis is considered an important candidate gene associated with psychiatric disorders. METHOD: Our sample consisted of 321 subjects (107 diagnosed with obsessive-compulsive disorder and 214 healthy controls), which were genotyped for eight tagSNPs (rs4448731, rs4565946, rs11179000, rs7955501, rs10506645, rs4760820, rs1487275 and rs10879357) covering the entire human tryptophan hydroxylase 2 gene. Statistical analyses were performed using UNPHASED, version 3.0.12, and Haploview ((R)). RESULTS: Single markers, genotype analysis did not show a significant genetic association with obsessive-compulsive disorder. A significant association between the T-C-T (rs4448731, rs4565946, rs10506645) and C-A-T (rs4565946, rs7955501, rs10506645) haplotypes and obsessive-compulsive disorder was observed, as well as a strong linkage disequilibrium between SNPs rs4448731 and rs4565946, and SNPs rs10506645 and 4760820. DISCUSSION: Our research has not demonstrated the existence of associations between the eight SNPs of TPH2 and obsessive-compulsive disorder. However, two LD and two haplotypes areas were demonstrated, thus suggesting that more studies in TPH2 are needed to investigate the role of tryptophan hydroxylase 2 variants in obsessive-compulsive disorder.

The relationship between the Met allele of the BDNF Val66Met polymorphism and impairments in decision making under ambiguity in patients with obsessive-compulsive disorder

“…For this reason, there has been renewed interest in the search for ‘endophenotypes’ (i.e. cognition dysfunctions), which are measurable disease‐associated traits that have a simpler relationship with underlying genes than with clinical measures (da Rocha et al in press).…”

Association of tryptophan hydroxylase-2 polymorphisms with oppositional defiant disorder in a Chinese Han population

“…Several studies have demonstrated that changes in the 5-HT system were critical in children with ODD [39, 40]. Moreover, the polymorphisms of TPH - 2 have been shown to be associated with ADHD [16, 41, 42], obsessive–compulsive disorder [43], and bipolar affective disorder [44]. Also, TPH -2 was found to be associated with major depression [45] and pathogenesis of depression in Chinese females [46] and suicidal behavior [47, 48].…”

Genetic and epigenetic architecture of Obsessive-Compulsive Disorder: In search of possible diagnostic and prognostic biomarkers

“…Some studies showed no significant differences in genotype frequency of the tryptophan hydroxylases TPH1 and TPH2 genes variants, encoding for the enzymes involved in serotonin synthesis (Delorme et al, 2006;Frisch et al, 2000;Han et al, 1999;Walitza et al, 2004). Conversely, other investigations reported haplotype association between TPH2 SNPs and the disorder (da Rocha et al, 2011;Mössner et al, 2006) or between rs4570625 and patients scrupulousness (Di Nocera et al, 2014).…”

“…rs4680 ( Val158Met) COMT (Catechol-O-Methyltransferase) polymorphism was associated with OCD (S. ), gender-specifically (Alsobrook et al, 2002Denys et al, 2006a;Karayiorgou et al, 1997Karayiorgou et al, , 1999Melo-Felippe et al, 2016;Pooley et al, 2007;Poyurovsky et al, 2005;Taylor, 2013), depending on the age at onset (Tükel et al, 2013) or Y-BOCS (Yale-Brown Obsessive-Compulsive Scalethe most frequently used interview to rate the severity of symptoms (Goodman et al, 1989)) scores (Erdal et al, 2003), or in patients with alexithymia tracts (Koh et al, 2016). However, other reports did not find an association between rs4680 and OCD (Bellivier et al, 1998;Camarena et al, 2004;Cristina Cavallini et al, 1998;da Rocha et al, 2011;Delorme et al, 2006;Di Bella et al, 2002;Han et al, 1999;Mak et al, 2015;Mössner et al, 2006;Walitza et al, 2002).…”