5' UTR polymorphism of dopamine receptor D1 (DRD1) associated with severity and temperament of alcoholism.
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.
Kim
Dai-Jin
DJ
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.
Park
Byung Lae
BL
Yoon
Sujung
S
Lee
Hae-Kook
HK
Joe
Keun-Ho
KH
Cheon
Young-Hoon
YH
Gwon
Do-Hoon
DH
Cho
Sung-Nam
SN
Lee
Hye Won
HW
NamGung
Suk
S
Shin
Hyoung Doo
HD
D020121:5' Untranslated Regions / Q000235:genetics*; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000145:classification / Q000453:epidemiology* / Q000235:genetics* / Q000523:psychology; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D012720:Severity of Illness Index
D020121:5' Untranslated Regions; D017447:Receptors, Dopamine D1