No coding variant of the tryptophan hydroxylase gene detected in seasonal affective disorder, obsessive-compulsive disorder, anorexia nervosa, and alcoholism

Background: The goal of this study was to evaluate the role of genetic vari ation in the coding sequence of tryptophan hydroxylase (TPH) in the pathoge nesis of several psychiatric diseases in which altered serotonin function h as been implicated: bipolar affective disorder (BP), obsessive-compulsive d isorder (OCD), anorexia nervosa (AN), seasonal affective disorder (SAD), pa nic disorder (PD), and alcoholism (Alc), Methods: Ninety-three percent of the TPH coding sequence was screened by po lymerase chain reaction single-strand conformation polymorphism (SSCP) for DNA sequence variations in 128 AN, 88 OCD, 72 SAD, 45 PD, and 36 BP patient s and 142 normal volunteers. Also included in the screening were 61 Ale ran domly selected from a Finnish alcoholic population in which art association of a TPH intron 7 polymorphism with suicidality was previously observed. P olymorphisms detected by SSCP were characterized by DNA sequencing and by a llele-specific restriction enzyme digestion. Genotyping was then performed in 34 Finnish alcoholic suicide attempters. Results: A rare silent mutation was identified in exon 10 and is designated T1095C. The C1095 allele was found in I OCD and in 2 AN subjects; all 3 in dividuals were heterozygous (C1095/T1095) for the variant allele. No associ ation was observed between this TPH T1095C variant with either OCD, AN, Ale , or suicidality. Conclusion: These results suggest that the coding sequence of the TPH gene does not contain abundant variants, and may not play a major role in vulner ability to several psychopathologies in which reduced serotonin turnover ha s been implicated. Biol Psychiatry 1999;45: 615-619 (C) 1999 Society of Bio logical Psychiatry.