Family‐based association study of TPH1 and TPH2 polymorphisms in autism

Abstract

The TPH1 and TPH2 genes encode the rate-limiting enzymes that control serotonin biosynthesis, and serotonin is clearly altered in autism. In the current study, eight SNPs in the TPH1 gene region and eight SNPs within the TPH2 gene were examined by family-based association tests in a large cohort of 352 families with autism and in clinically defined subsets of these families with either severe obsessive-compulsive behaviors (sOCB) or self-stimulatory behaviors (SSB). We found no evidence for association between autism and single SNPs or haplotypes of the TPH1 and TPH2 genes in the cohort of all families or in the sOCB and SSB subsets. In particular, we failed to replicate the association between autism and variants of the TPH2 gene, rs4341581 (TRANSMIT P = 1; PDT P = 0.323; FBAT P = 0.446) and rs11179000 (TRANSMIT P = 0.174; PDT P = 0.293; FBAT P = 0.374). Furthermore, no evidence for linkage was observed between autism and SNPs in the TPH1 and TPH2 genes (although linkage at the TPH2 locus was observed in the SSB subset). Thus, it appears unlikely that the TPH1 and TPH2 genes play a significant role in the susceptibility to autism or to autism endophenotypes including sOCB and SSB.

Molecular and genetic basis of depression

“…TPH2 has been shown to be associated with the pathophysiology of several psychiatric disorders such as anxiety, aggression, depression-associated personality traits, suicidal behaviour, bipolar disorder, attention deficit hyperactivity disorder and deficits in cognitive control and emotion (Waider et al 2011). A rare variant of TPH2 (rs120074175) showed its association with the psychiatric disorders (Zhang et al 2005), however, several studies failed to establish this association (Delorme et al 2006;Ramoz et al 2006;Sacco et al 2007). TPH1 is an isoform of TPH2 sharing 70% homology in amino acid sequence and expressed in the gastrointestinal tract and pineal gland (Walther and Bader 2003).…”

An analysis of candidate autism loci on chromosome 2q24–q33: Evidence for association to the STK39 gene

“…Among the siblings, 37 subjects assessed with borderline autism were considered affected while 41 siblings assessed with broad spectrum and/or PDD-NOS were not considered as affected in the current study. The ethnicity status was as previously described [Ramoz et al, 2006].…”

Modulations of Mammalian Brain Functions by Antidepressant Drugs: Role of Some Phytochemicals as Prospective Antidepressants

“…TPH2 has been shown to be associated with the several depressive disorders such as depressionassociated personality traits, anxiety, bipolar disorder, aggression, and suicide, deficits in cognitive control and emotion and attention deficit hyperactivity disorder [95]. TPH2 variant (rs120074175) has been shown to be associated with the depression [96], but studies in further years failed to establish this association [97][98][99]. TPH1, an isoform of TPH2 expressed in the gastrointestinal tract and pineal gland [100], has been reported that rs2108977 of TPH1 is associated with hyperphagia, posttraumatic stress disorder (PTSD), higher level of anxiety and depression.…”