Investigation of the tryptophan hydroxylase 2 gene in bipolar I disorder in the Romanian population

Objective Since the discovery of the tryptophan hydroxylase 2 gene (TPH2) several studies reported the association of TPH2 genetic variation with bipolar I (BPI) disorder. Our first objective was to replicate the recently described association of a rare functional single nucleotide polymorphism (SNP) (rs17110563) and of a haplotype covering the 5′ region of TPH2 with BPI in a sample from the Romanian population. The second objective was 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. Method 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 Haploview v.3.32 and FAMHAP. Results The functional SNP rs17110563 (encoding a Pro206Ser substitution) was present in one Romanian BPI patient and absent in controls. SNPs located in the 5′-region (rs11178997, rs11178998, rs7954758) that had earlier been found to be significantly associated with BPI in a German sample were not associated with BPI in the overall Romanian sample at the single-marker level, but gave evidence for association in a subgroup of patients with paternal transmission of the disease at the haplotypic level. Further evidence of 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 patient group with paternal transmission, and the patient group with age of onset below or equal to 25 years. Conclusion These data provide further support for the involvement of genetic variation in TPH2 in the etiology of BPI.