A European multicenter association study of HTR2A receptor polymorphism inbipolar affective disorder

The available data on the role of 5-HT in a variety of behaviors support th e hypothesis that a dysfunction in brain serotoninergic system activity con tributes to vulnerability to major depression. The diversity in the electro physiological actions of 5-HT in the central nervous system can now be cate gorized according to receptor subtypes and their respective effector mechan isms. In particular, the implication of central postsynaptic 5-HT2A recepto r in affective disorders has been supported by findings consistent with the hypothesis of 5-HT2A receptor up-regulation in depression. For these reaso ns, the 5-HT2A receptor (HTR2A) gene can be considered as a candidate gene in bipolar affective disorder (BPAD), We tested the possible genetic contri bution of the polymorphic DNA variation T102C in exon 1 of HTR2A (chromosom e 13q14-21) gene in a large European multicentric case-control sample. Alle le and genotype frequencies, as well as homo-heterozygote distributions wer e compared between the two groups of 309 bipolar affective disorder patient s and 309 matched controls. No significant differences were observed in the allelic and genotypic (also for homo-heterozygote) distribution between BP AD and controls. These results indicate that, in our sample, the 5-HT2A rec eptor polymorphism studied is unlikely to play a major role in the genetic susceptibility to BPAD, (C) 2000 Wiley-Liss, Inc.