Nine- or fewer repeat alleles in VNTR polymorphism of the dopamine transporter gene is a strong risk factor for prolonged methamphetamine psychosis
Nine- or fewer repeat alleles in VNTR polymorphism of the dopamine transporter gene is a strong risk factor for prolonged methamphetamine psychosis
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DOI：
10.1038/sj.tpj.6500189
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发表时间：
2003-01-01
影响因子：
2.8
通讯作者：
Ozaki, N
中科院分区：
文献类型：
--
作者：
Ujike, H;Harano, M;Ozaki, N
对药物依赖和药物引起的精神病的易感性不仅受到药物药理作用的影响，而且还受到个人遗传因素的影响。为了澄清后者，我们研究了甲基苯丙胺（METH）依赖/精神病与编码多巴胺转运蛋白的hDAT 1基因（SLC 6A 3）之间的关联，该基因是大脑中METH活性的主要位点。检测hDAT 1基因外显子2、9、3 'UTR、242 C/T、1342 A/G、2319 G/A四个外显子的多态性。尽管所有METH依赖/精神病患者（N=124）和对照组（N=160）之间四种多态性的基因型和等位基因分布没有显著差异，但在停止METH消耗后持续1个月或更长时间的METH精神病患者显示hDAT 1基因的3 'UTR中VNTR的9个或更少重复等位基因显著过量（P=0.0054，OR=4.24，95%CI =2.46-7.31）。目前的研究表明，存在9个或更少的重复等位基因的hDAT 1是一个很强的危险因素，METH精神病的预后较差。
Susceptibility to drug dependence and drug-induced psychoses is influenced not only by the pharmacological effects of the drug but also by the genetic factors of the individual. To clarify the latter, we investigated the association between methamphetamine (METH) dependence/psychosis and the hDAT1 gene (SLC6A3) encoding the dopamine transporter, which is the primary site of METH activity in the brain. Four exonic polymorphisms of the hDAT1 gene, 242C/T (exon 2), 1342A/G (exon 9), 2319G/A (3'UTR), and VNTR (3'UTR) were examined. Although there was no significant difference in genotypic and allelic distribution of the four polymorphisms between all METH dependence/psychosis patients (N=124) and controls (N=160), the patients with METH psychosis lasting for 1 month or more after discontinuance of METH consumption showed a significant excess of nine- or fewer repeat alleles of the VNTR in 3'UTR of the hDAT1 gene (P=0.0054, OR=4.24, 95% CI=2.46-7.31). The present study demonstrated that the presence of nine- or fewer repeat alleles of hDAT1 is a strong risk factor for a worse prognosis of METH psychosis.