Association of Alcohol Use Disorder Risk With ADH1B, DRD2, FAAH, SLC39A8, GCKR, and PDYN Genetic Polymorphisms

Alcohol use disorder (AUD) is a chronic, multifactorial psychiatric condition with an enormous impact on public health and social cost. Genetic studies suggest a heritability, and genome-wide association studies (GWAS) have revealed genetic polymorphisms influencing AUD development. Our study aimed to investigate known variants located in ADH1B, DRD2, FAAH, SLC39A8, GCKR, and PDYN genes (rs1229984, rs7121986, rs324420, rs13107325, rs1260326, rs2281285 respectively) in an AUD Greek cohort in order to shed more light on the genetic predisposition to AUD.

Alcohol-dependent individuals (n=251) meeting both the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the ICD-10 guidelines for alcohol abuse and dependence, and control individuals (n=280) were recruited. DNA was extracted from whole blood and PCR-restriction fragment length polymorphism (RFLP-PCR) or allele-specific PCR method was used for genotyping.

Individuals carrying the FAAH rs324420 A allele were significantly associated with increased risk of AUD (p<0.0001). SLC39A8 rs13107325 T allele and ADH1B rs1229984 T allele are overrepresented in control subjects (p<0.0001 and p<0.0001, respectively). The associations are maintained following an adjustment for age and sex and Bonferroni correction. GCKR rs13107325, DRD2 rs7121986, and PDYN rs2281285 polymorphisms did not show a significant association with AUD in the studied population after Bonferroni correction.

Susceptibility to AUD is related to variations in FAAH, ADH1B, and SLC39A8 genes. These polymorphisms could serve as potential biomarkers for AUD risk.