Serotonin transporter gene polymorphism influences age at onset in patients with bipolar affective disorder

Serotonin transporter (SLC6A4) gene polymorphism is associated with several behavioral and psychiatric traits. In bipolar affective disorder, two polymorphisms of the SLC6A4 gene, a variable number of tandem repeats in the second intron and a 44 bp insertion/deletion in the serotonin transporter gene linked polymorphic region (5-HTTLPR), have been extensively studied. The findings are conflicting possibly because of the heterogeneity of bipolar disorder. Early-onset bipolar disorder appears to be clinically and genetically more homogeneous and was recently suggested to be associated with the 5-HTTLPR polymorphism. We tested the association between two polymorphisms of the SLC6A4 gene and age at onset (AAO) in a sample of bipolar patients. For both SLC6A4 gene polymorphisms, AAO of subjects with different genotypes were compared. SLC6A4 genotype distributions of different AAO groups were also compared. The variable number of tandem repeats (VNTR) polymorphism significantly influences the AAO but the serotonin transporter gene linked polymorphic region (5-HTTLPR) polymorphism did not. Patients carrying at least one VNTR STin2.12 allele began their illness later whereas patients carrying the 'ss' genotype tended to begin their illness earlier. Differential sampling procedures may influence the proportion of AAO subgroups in a given association study, and therefore these results may explain the conflicting results obtained in studies of the association between the SLC6A4 gene polymorphism and bipolar affective disorder (BPAD).