Serotonin-related gene polymorphisms and central nervous system serotonin function

Abstract

Centralnervous system (CNS) serotonergic function affects a wide range of biologicaland behavioralfunctions affecting health and disease. Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the serotonin transporter promoter (5HTTLPR) and monoamine oxidase A (MAOA-uVNTR) are associated with CNS serotonin turnover—indexed by cerebrospinalfluid levels of 5-hydroxyindoleacetic acid (5-HIAA)—in a community sample of healthy adults. Subjects were 165 community volunteers without current medicalor psychiatric illness, stratified with respect to ethnicity, gender, and socioeconomic status who underwent inpatient evaluation in the GeneralClinicalResearch Center of a university medicalcenter. A significant ethnicity x genotype interaction (P = 0.008) indicated that, compared to the long/long and long/short genotypes, the 5HTTLPR short/short genotype was associated with higher CSF 5-HIAA levels in African Americans, but with lower levels in Caucasians. A gender x genotype interaction (P = 0.04) indicated that 5HTTLPR short/short genotype was associated with higher 5-HIAA levels in women but with lower levels in men. MAOA-uVNTR 3.5 and 4 repeat alleles were associated with higher 5-HIAA (P = 0.03) levels in men, but were unrelated to 5-HIAA levels in women. These findings suggest that effects of serotonin-related gene polymorphisms on CNS serotonergic function vary as a function of both ethnicity and gender. Further research willbe required to determine the mechanism(s) underlying these differentialeffects. In the meanwhile, both ethnicity and gender should be taken into account in research evaluating effects of these and related polymorphisms on CNS serotonergic function, as wellas the broad range of biologicaland behavioralfunctions that are regulated by CNS serotonergic function. © 2003 Nature Publishing Group.