5′ UTR polymorphism of dopamine receptor D1 (DRD1) associated with severity and temperament of alcoholism

Dai Jin Kim, Byung Lae Park, Sujung Yoon, Hae Kook Lee, Keun Ho Joe, Young Hoon Cheon, Do Hoon Gwon, Sung Nam Cho, Hye Won Lee, Suk NamGung, Hyoung Doo Shin

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47 Scopus citations

Abstract

Multiple dopamine receptors in the dopaminergic system may be prime candidates for genetic influence on alcohol abuse and dependence due to their involvement in reward and reinforcing mechanisms. Genetic polymorphisms in dopamine receptor genes are believed to influence the development and/or severity of alcoholism. To examine the genetic effects of the Dopamine Receptor D1 (DRD) gene family (DRD1-DRD5) in the Korean population, 11 polymorphisms in the DRD gene family were genotyped and analyzed in 535 alcohol-dependent subjects and 273 population controls. Although none of the polymorphisms of DRD1-5 genes were found to be associated with the risk of alcoholism, one 5′ UTR polymorphism in the DRD1 (DRD1-48A>G) gene was significantly associated with severity of alcohol-related problem, as measured by the Alcohol Use Disorders Identification Test (AUDIT) in a gene dose-dependent manner, i.e., 24.37 (±8.19) among patients with -48A/A genotype, 22.37 (±9.49) among those with -48A/G genotype, and 17.38 (±8.28) among those with -48G/G genotype (P = 0.002). The genetic effects of DRD1-48A>G were further analyzed with other phenotypes among alcohol-dependent subjects. Interestingly, the DRD1-48A>A genotype was also found to be associated with novelty seeking (NC), harm avoidance (HA), and persistence (P) (P = 0.01, 0.02, and 0.003, respectively). The information derived from this study could be valuable for understanding the genetic factors involved in alcoholic phenotypes and genetic distribution of the DRD gene family, and could facilitate further investigation in other ethnic groups.

Original languageEnglish
Pages (from-to)1135-1141
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume357
Issue number4
DOIs
StatePublished - 15 Jun 2007

Bibliographical note

Funding Information:
This study was supported by a grant of the Korea Health 21 R&D Project. Ministry of Health & Welfare, Republic of Korea (03-PJ10-PG13-GD01-0002), a grant from Biomedical Brain Research Center of the Korea Health 21 R&D Project funded by the Ministry of Health & Welfare, Republic of Korea (A040042) and a grant from the National Research Lab Program as part of the National Research and Development Program from the Ministry of Industry and Energy of Korea, contract grant number M1-0302-00-0073.

Keywords

  • AUDIT
  • DRD gene family
  • Korean population
  • Risk of alcoholism
  • Severity
  • Single nucleotide polymorphism (SNP)
  • Temperament

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