Variations in the vesicular monoamine transporter 1 gene (VMAT1/SLC18A1) are associated with bipolar i disorder.

The vesicular monoamine transporter 1 gene (VMAT1/SLC18A1) maps to the shared bipolar disorder (BPD)/schizophrenia (SZ) susceptibility locus on chromosome 8p21. Vesicular monoamine transporters are involved in transport of monoamine neurotransmitters which have been postulated to play a relevant role in the etiology of BPD and/or SZ. Variations in the VMAT1 gene might affect transporter function and/or expression and might be involved in the etiology of BPD and/or SZ. Genotypes of 585 patients with BPD type I and 563 control subjects were obtained for three missense single nucleotide polymorphisms (SNPs) (Thr4Pro, Thr98Ser, Thr136Ile) and four non-coding SNPs (rs988713, rs2279709, rs3735835, rs1497020). All cases and controls were of European descent. Allele frequencies differed significantly for the potential functional polymorphism Thr136Ser between BPD patients and controls (p=0.003; df=1; OR=1.34; 95% CI: 1.11-1.62). Polymorphisms in the promoter region (rs988713: p=0.005, df=1; OR=1.31; 95% CI: 1.09-1.59) and intron 8 (rs2279709: p=0.039, df=1; OR=0.84; 95% CI: 0.71-0.99) were also associated with disease. Expression analysis confirmed that VMAT1 is expressed in human brain at the mRNA and protein level. Results suggest that variations in the VMAT1 gene may confer susceptibility to BPD in patients of European descent. Additional studies are necessary to confirm this effect and to elucidate the role of VMAT1 in central nervous system physiology.