Association analysis of the DRD4 and COMT genes in methamphetamine abuse

Tao Li, Chi Ken Chen, Xun Hu, David Ball, Shih Ku Lin, Wai Chen, Pak C. Sham, El Wui Loh, Robin M. Murray, David A. Collier

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92 引文 斯高帕斯(Scopus)

摘要

We analyzed two polymorphisms in genes encoding proteins of the dopamine system, the Val158Met polymorphism in the catechol-O-methyltransferase gene and the 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene for association with methamphetamine abuse. We used a case/control design with 416 methamphetamine abusing subjects and 435 normal controls. All subjects were Han Chinese from Taiwan. We found an excess of the high activity Val158 allele in the methamphetamine abuser group, consistent with several previous reports of association of this allele with drug abuse. The 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene itself did not show significant association with methamphetamine abuse. However, analysis of the 120-bp VNTR polymorphism and the exon 3 VNTR in the dopamine D4 receptor as a haplotype showed significant association with methamphetamine abuse, which gave an empirical P value 0.0034 for a heterogeneity model. Moreover, there were significant interactive effects between polymorphisms in the catechol-O-methyltransferase and dopamine D4 genes. The evidence of interaction between COMT 158 Val/Met and DRD4 48-bp VNTR polymorphisms (P = 0.0003, OR = 1.45, 95% CI: 1.148-1.77), and between COMT 158 Val/Met and DRD4 120 bp promoter polymorphisms (P = 0.01, OR = 1.10, 95% CI: 1.10-1.18) were significant but the latter was weak. We conclude that genetic variation in the dopamine system may encode an additive effect on risk of becoming a methamphetamine abuser.
原文英語
頁(從 - 到)120-124
頁數5
期刊American Journal of Medical Genetics - Neuropsychiatric Genetics
129 B
發行號1
出版狀態已發佈 - 八月 15 2004
對外發佈

ASJC Scopus subject areas

  • 遺傳學(臨床)
  • 精神病學和心理健康
  • 細胞與分子神經科學

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