Association between gene polymorphisms of SLC22A3 and methamphetamine use disorder
Association between gene polymorphisms of SLC22A3 and methamphetamine use disorder
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DOI：
10.1111/j.1530-0277.2006.00215.x
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发表时间：
2006-10-01
影响因子：
3.2
通讯作者：
Ozaki, Norio
中科院分区：
文献类型：
--
作者：
Aoyama, Nagisa;Takahashi, Nagahide;Ozaki, Norio
背景资料：甲基苯丙胺（MAP）是日本最常用的非法药物之一，家庭和双胞胎研究表明，遗传因素有助于精神兴奋剂依赖，包括MAP依赖。有机阳离子转运蛋白3（OCT3）已被报道参与MAP的处置以及MAP诱导的动物行为变化。此外，SLC22A3（OCT3编码）是一个候选基因的MAP依赖，因为它是位于染色体区域内与物质dependance.Methods：使用96名健康对照，连锁不平衡（LD）内的SLC22A3进行了调查，并选择5个单核苷酸多态性（SNPs）作为单倍型标签SNPs搜索与MAP依赖的关联。对213例MAP依赖者和443例健康对照者进行单标记分析和单倍型分析。将MAP依赖者分为多种物质依赖者和单一MAP依赖者，（p=0.024，p=0.011），SNP3等位基因频率（p=0.037），以及这2个SNP的单倍型频率（p=0.0438）组间差异显著。这些结果表明，SLC22A3的多态性与MAP依赖的日本患者使用多种药物的发展有关。
Background: Methamphetamine (MAP) is one of the most frequently used illegal substances in Japan, and family and twin studies have suggested that genetic factors contribute to psychostimulant dependence, including MAP dependence. Organic cation transporter 3 (OCT3) has been reported to be involved in the disposition of MAP as well as MAP-induced behavioral changes in animals. Moreover, SLC22A3 (which encodes OCT3) is a candidate gene for MAP dependence because it is located within a chromosomal region associated with substance dependence.Methods: Using 96 healthy control subjects, linkage disequilibrium (LD) within the SLC22A3 was investigated, and 5 single-nucleotide polymorphisms (SNPs) were selected as haplotype tag SNPs to search for an association with MAP dependence. Single-marker analyses and haplotype analyses of these SNPs were performed in 213 subjects with MAP dependence and 443 healthy controls.Results: SLC22A3 polymorphisms were not significantly associated with MAP dependence in any of the single-marker and haplotype analyses. When subjects with MAP dependence were divided into polysubstance and single-MAP users, genotype and allele frequency of SNP2 (p=0.024, p=0.011, respectively), allele frequency of SNP3 (p=0.037), and haplotypic frequencies for these 2 SNPs (p=0.0438) differed significantly between groups.Conclusions: These results suggest that polymorphisms of SLC22A3 are related to the development of polysubstance use in Japanese patients with MAP dependence.