DNA variation and psychopharmacology of the human serotonin receptor 1B (HTR1B) gene

Abstract

One of the neurotransmitter serotonin's receptors, HTR1B, is of interest for many neuropsychiatric traits, illnesses and treatments for multiple reasons, especially its tissue distribution, pharmacological profile and findings from mice lacking the receptor, along with reasons generally implicating serotonin. Eight mutation scans have uncovered sixteen polymorphisms in the coding sequence and surrounding 5'- and 3'-untranslated regions and much is now known of the distribution of these polymorphisms in various ethnic groups and their linkage disequilibrium relationships. Thus far, evidence exists that the uncommon missense T371G (Phe124Cys) and the common promoter region A-161T polymorphisms may exhibit functional effects and possibly that the common synonymous G861C (or more likely a variant in linkage disequilibrium with G861C) does as well. From the eighteen reported population-based case control studies of HTR1B to multiple disorders, several facts stand out. There exists preliminary evidence for association of G861C with i) antisocial alcoholism in the Finnish; ii) alcoholism in the presence of inactive aldehyde dehydrogenase 2 in the Japanese; iii) a history of suicide attempts in European-American personality disorder patients; and iv) minimum lifetime body mass index in Canadian bulimia nervosa patients. From the three reported family-based case control studies of HTR1B to various disorders, one provides preliminary evidence for association of G861C with obsessive compulsive disorder. Although many association studies have been completed, positive results should still be considered preliminary. As these preliminary reports are tested for replication with larger, more powerful samples, there should be increased clarity as to which findings remain robust; in some cases this will require the application of meta-analytic techniques.