DRD3 Gene rs6280 Polymorphism May Be Associated with Alcohol Dependence Overall and with Lesch Type I Alcohol Dependence in Koreans

Abstract

Background: Several polymorphisms of the dopamine D₃ receptor (DRD3) gene are reported to be involved in the susceptibility to alcoholism. Although the DRD3 rs6280 (Ser9Gly) polymorphism plays an important role in various psychiatric disorders, findings regarding the association between this single-nucleotide polymorphism (SNP) and alcohol dependence (AD) have been inconsistent. Therefore, the present study investigated the association between the DRD3 gene rs6280 polymorphism with AD and Lesch type I AD in Korean subjects. Methods: The DRD3 rs6280 SNP was genotyped in a case-control sample comprising 245 AD patients and 130 healthy controls (HCs). Alcohol Use Disorders Identification Test (AUDIT) scores were also compared relative to genotype in all of the participants. Results: This SNP was significantly associated with both AD overall (χ² = 10.09 and p = 0.001, and χ² = 10.60 and p = 0.005, for the recessive and additive models, respectively) and with Lesch type I AD (χ² = 11.70 and p = 0.001, and χ² = 11.70 and p = 0.003, for the recessive and additive models, respectively). The allele frequency differed significantly (χ² = 8.45, p = 0.004) between Lesch type I AD and HC subjects. The AUDIT total (F = 6.56, p = 0.011), hazardous alcohol use (F = 7.12, p = 0.008), dependence symptoms (F = 5.10, p = 0.025), and harmful alcohol use (F = 4.83, p = 0.029) scores were significantly higher in those who did not possess the S allele (genotype GG) than in those who did (genotypes SS ± SG). Conclusions: The findings of this study suggest that the DRD3 rs6280 polymorphism is associated with the development of both AD overall and Lesch type I AD in Koreans.