| Summary: | <p>Abstract</p> <p>Background</p> <p>Disturbances in serotonin neurotransmission are implicated in the etiology of many psychiatric disorders, including bipolar affective disorder (BPD). The tryptophan hydroxylase gene (<it>TPH</it>), which codes for the enzyme catalyzing the rate-limiting step in serotonin biosynthetic pathway, is one of the leading candidate genes for psychiatric and behavioral disorders. In a preliminary study, we found that <it>TPH1 </it>intron7 A218C polymorphism was associated with BPD. This study was designed to investigate sequence variants of the <it>TPH1 </it>gene in Taiwanese and to test whether the <it>TPH1 </it>gene is a susceptibility factor for the BPD.</p> <p>Methods</p> <p>Using a systematic approach, we have searched the exons and promoter region of the <it>TPH1 </it>gene for sequence variants in Taiwanese Han and have identified five variants, A-1067G, G-347T, T3804A, C27224T, and A27237G. These five variants plus another five taken from the literature and a public database were examined for an association in 108 BPD patients and 103 controls; no association was detected for any of the 10 variants.</p> <p>Results</p> <p>Haplotype constructions using these 10 SNPs showed that the 3 most common haplotypes in both patients and controls were identical. One of the fourth common haplotype in the patient group (i.e. GGGAGACCCA) was unique and showed a trend of significance with the disease (P = 0.028). However, the significance was abolished after Bonferroni correction thus suggesting the association is weak. In addition, three haplotype-tagged SNPs (htSNPs) were selected to represent all haplotypes with frequencies larger than 2% in the Taiwanese Han population. The defined <it>TPH1 </it>htSNPs significantly reduce the marker number for haplotype analysis thus provides useful information for future association studies in our population.</p> <p>Conclusion</p> <p>Results of this study did not support the role of <it>TPH1 </it>gene in BPD etiology. As the current studies found the <it>TPH1 </it>gene under investigation belongs to the peripheral serotonin system and may link to a cardiac dysfunction phenotype, a second TPH gene that functions predominantly in the brain (i.e., nTPH or TPH2) should be the target for the future association study.</p>
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