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：
10.1097/00004850-200607000-00095
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发表时间：
2006-07
期刊：
影响因子：
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通讯作者：
Nagisa Aoyama;N. Takahashi;K. Kitaichi;R. Ishihara;S. Saito;N. Maeno;Xiaofei Ji;K. Takagi;Y. Sekine;M. Iyo;M. Harano;T. Komiyama;M. Yamada;I. Sora;H. Ujike;N. Iwata;T. Inada;N. Ozaki
中科院分区：
文献类型：
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作者：
Nagisa Aoyama;N. Takahashi;K. Kitaichi;R. Ishihara;S. Saito;N. Maeno;Xiaofei Ji;K. Takagi;Y. Sekine;M. Iyo;M. Harano;T. Komiyama;M. Yamada;I. Sora;H. Ujike;N. Iwata;T. Inada;N. Ozaki
背景甲基苯丙胺(MAP)是日本使用最频繁的非法物质之一，家族和双胞胎研究表明，遗传因素导致精神刺激依赖，包括MAP依赖。据报道，有机阳离子转运蛋白3(Oct3)参与了MAP的处置以及MAP诱导的动物行为改变。此外，SLC22A3(编码Oct3)是MAP依赖的候选基因，因为它位于与物质依赖相关的染色体区域。方法对96例健康对照人群进行SLC22A3基因连锁不平衡分析，选择5个单核苷酸多态(SNPs)作为单倍型标签SNPs，寻找与MAP依赖相关的基因。对213例MAP依赖者和443例健康对照进行了这些SNPs的单标记和单倍型分析。结果在单标记和单倍型分析中，SLC22A3基因多态性与MAP相关性均不显著。当MAP依赖患者分为多物质使用者和单一MAP使用者时，两组间SNP2的等位基因频率(p=0.024，p=0.011)、SNP3的等位基因频率(p=0.037)和单倍型频率(p=0.0438)差异均有统计学意义。结论SLC22A3基因多态性与日本MAP依赖患者多物质使用的发生有关。
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.