Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders: A multicenter association study

Background: Being the rate-limiting enzyme in the biosynthesis of serotonin , the tryptophan hydroxylase gene (TPH) has been considered a possible cand idate gene in bipolar and unipolar affective disorders (BPAD and UPAD). Sev eral studies have investigated the possible role of TPH polymorphisms in af fective disorders and suicidal behavior. Methods: The TPH A218C polymorphism has been investigated in 927 patients ( 527 BPAD and 400 UPAD) and their matched healthy control subjects collected within the European Collaborative Project on Affective Disorders. Results: No difference of genotype distribution or allele distribution was found in BPAD or UPAD. No statistically significance difference was observe d for allele frequency and genotypes counts. In a genotype per genotype ana lysis in UPAD patients with a personal history of suicide attempt, the freq uency of the C-C genotype (homozygosity for the short allele) was lower in UPAD patients (24%) than in control subjects (43%) (chi (2) = 4.67, p = .03 ). There was no difference in allele or genotype frequency between patients presenting violent suicidal behavior (n = 48) and their matched control su bjects. Conclusions: We failed to detect an association between the A218C polymorph ism of the TPH gene and BPAD and UPAD in a large European sample. Homozygos ity for the short allele is significantly less frequent in a subgroup of UP AD patients with a history of suicide attempt than in control subject. Biol Psychiatry 2001;49:405-409 (C) 2001 Society of Biological Psychiatry.