Lohoff Falk W, Weller Andrew E, Bloch Paul J, Buono Russell J, Doyle Glenn A, Ferraro Thomas N, Berrettini Wade H
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Neuropsychobiology. 2008;57(1-2):55-60. doi: 10.1159/000129668. Epub 2008 May 2.
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.
连锁研究表明，8号染色体p21-22区域存在一个精神分裂症（SZ）易感基因座。囊泡单胺转运体1基因（VMAT1），也称为SLC18A1，定位于该SZ易感基因座。囊泡单胺转运体参与单胺类神经递质的突触前囊泡包装，据推测这在SZ的病因学中起作用。VMAT1基因的变异可能影响转运体功能和/或表达，并可能参与SZ的病因学。对62例SZ患者和188例对照者进行了4个错义单核苷酸多态性（Thr4Pro、Thr98Ser、Thr136Ile、Val392Leu）和2个非编码单核苷酸多态性（rs988713、rs2279709）的基因分型。所有病例和对照均为欧洲血统。与对照相比，SZ患者中Thr4Pro多态性次要等位基因的频率显著增加（p = 0.0140；自由度 = 1；优势比 = 1.69；95%可信区间 = 1.11 - 2.57）。假设为隐性遗传模式，与对照相比，SZ患者中纯合子4Pro携带者的频率显著增加（分别为24%和8%；p = 0.0006；自由度 = 1；优势比 = 3.74；95%可信区间 = 1.703 - 8.21）。单倍型分析显示一个个体风险单倍型具有名义显著性（p = 0.013）；然而，经过排列校正后，全局p值未达到统计学显著水平（p = 0.07）。结果表明，VMAT1基因的变异可能使欧洲血统的患者易患SZ。需要进一步研究来证实这种效应，并阐明VMAT1在中枢神经系统生理学中的作用以及可能参与SZ的遗传起源。
