5' UTR polymorphism of dopamine receptor D1 (DRD1) associated with severity and temperament of alcoholism |
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Authors: | Kim Dai-Jin Park Byung Lae Yoon Sujung Lee Hae-Kook Joe Keun-Ho Cheon Young-Hoon Gwon Do-Hoon Cho Sung-Nam Lee Hye Won NamGung Suk Shin Hyoung Doo |
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Affiliation: | Department of Psychiatry, Holy Family Hospital, College of Medicine, Catholic University of Korea, Sosa-dong, Wonmi-Gu, Pucheon, Kyounggi-do 420-717, Republic of Korea. |
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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. |
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Keywords: | DRD gene family AUDIT Severity Temperament Single nucleotide polymorphism (SNP) Risk of alcoholism Korean population |
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