title: Association between polymorphisms in the vesicular monoamine transporter 1 gene (VMAT1/SLC18A1) on chromosome 8p and schizophrenia.
abstract: Linkage studies have suggested a susceptibility locus for schizophrenia (SZ) exists on chromosome 8p21-22. The vesicular monoamine transporter 1 gene (VMAT1), also known as SLC18A1, maps to this SZ susceptibility locus. Vesicular monoamine transporters are involved in the presynaptic vesicular packaging of monoamine neurotransmitters, which have been postulated to play a role in the etiology of SZ. Variations in the VMAT1 gene might affect transporter function and/or expression, and might be involved in the etiology of SZ. Genotypes of 62 patients with SZ and 188 control subjects were obtained for 4 missense single nucleotide polymorphisms (Thr4Pro, Thr98Ser, Thr136Ile, Val392Leu) and 2 noncoding single nucleotide polymorphisms (rs988713, rs2279709). All cases and controls were of European descent. The frequency of the minor allele of the Thr4Pro polymorphism was significantly increased in SZ patients when compared to controls (p = 0.0140; d.f. = 1; OR = 1.69; 95% CI = 1.11-2.57). Assuming a recessive mode of inheritance, the frequency of homozygote 4Pro carriers was significantly increased in the SZ patients when compared to controls (24 vs. 8%, respectively; p = 0.0006; d.f. = 1; OR = 3.74; 95% CI = 1.703-8.21). Haplotype analysis showed nominal significance for an individual risk haplotype (p = 0.013); however, after permutation correction, the global p value did not attain a statistically significant level (p = 0.07). Results suggest that variations in the VMAT1 gene may confer susceptibility to SZ in patients of European descent. Further studies are necessary to confirm this effect, and to elucidate the role of VMAT1 in central nervous system physiology and possible involvement in the genetic origins of SZ.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA. lohoff@mail.med.upenn.edu
authors.forename: Falk W
authors.initials: FW
authors.lastname: Lohoff
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Weller
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bloch
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Buono
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Doyle
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Ferraro
authors.forename: Wade H
authors.initials: WH
authors.lastname: Berrettini
mesh_terms: D000328:Adult; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D020890:Neuregulin-1; D011110:Polymorphism, Genetic / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics*
chemical_list: C094131:NRG1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; C493449:SLC18A1 protein, human; D050493:Vesicular Monoamine Transport Proteins