Since the discovery of the tryptophan hydroxylase 2 gene (TPH2) several studies reported association of TPH2 genetic variation with bipolar I disorder (BPI). Our objectives were to replicate in the Romanian population the recently described association of a rare functional SNP (rs17110563) and of a haplotype covering the 5′ region of TPH2 with BPI (Cichon et al., 2008) and to investigate the influence of the phenotypic traits age-of-onset, family history and parent-of-origin”, defined according to clinical criteria, on the degree of association between TPH2 and BPI.

Sixteen TPH2 SNPs were genotyped in a Romanian sample of 198 BPI patients and 180 controls screened for psychiatric disorders. Statistical analysis of the data was performed with Haploview3.32 and FAMHAP.

The functional SNP rs17110563 (encoding a Pro206Ser substitution) was present in Romanian BPI patients and absent in controls. SNPs located in the 5′-region (rs11178997, rs11178998, rs7954758), significantly associated with BPI in German patients were not associated with BPI in Romanian patients at single-marker level, but gave evidence for association at haplotypic level in a subgroup of patients with paternal transmission of BPI. Evidence for association was identified between haplotypes located in the 3′-region of TPH2 and BPI in the overall sample as well as in the subgroups of familial cases, the subgroup with paternal transmission, and the subgroup with AO≤25 years.

Our data provide support for the involvement of TPH2 in the etiology of BPI.