Effect of PDYN and OPRK1 polymorphisms on the risk of alcohol use disorder and the intensity of depressive symptoms

Alcohol Alcohol. 2023 Jul 10;58(4):404-414. doi: 10.1093/alcalc/agad036.

Abstract

Aims: The dynorphin (DYN)/Kappa Opioid Receptor (KOR) system has been suggested to be involved in both negative affective states and the action of alcohol. The present study was undertaken to explore whether the DYN/KOR system genes, PDYN and OPRK1, influence on individual differences in the intensity of depressive symptoms at admission as well as the risk of alcohol use disorder (AUD) risk in a sample of 101 individuals with AUD and 100 controls.

Methods: PDYN (rs2281285, rs2225749 and rs910080) and OPRK1 (rs6473797, rs963549 and rs997917) polymorphisms were analyzed by PCR-RFLP. The intensity of depressive and anxiety symptoms and craving were measured by the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and Penn Alcohol Craving Scale, respectively.

Results: A significant association between the risk of AUD and OPRK1 rs6473797 (P < 0.05) at the gene level. OPRK1 rs6473797 CC genotype was found to lead to a 3.11 times greater alcohol dependence risk. In addition, the BDI-II score of the OPRK1 rs963549 CC genotype was found to be significantly lower (20.9 ± 11.2, min: 1.0, max: 48.0) than that of the CT + TT genotypes (27.04 ± 12.7, min: 0.0, max: 49.0) (t: -2.332, P = 0.022). None of the PDYN polymorphisms were associated with BDI-II score.

Conclusion: Variations in the KOR are associated with the risk of AUD and the intensity of depressive symptoms at admission at the gene level in Turkish males. On the other hand, PDYN gene seemed not to be associated with AUD, depression, anxiety, and craving.

Keywords: OPRK1 rs6473797; OPRK1 rs963549; alcohol use disorder; individual difference; kappa-opioid receptor.

MeSH terms

  • Alcoholism* / complications
  • Alcoholism* / genetics
  • Depression / genetics
  • Ethanol
  • Genotype
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, Opioid, kappa / genetics

Substances

  • Ethanol
  • OPRK1 protein, human
  • Receptors, Opioid, kappa
  • preproenkephalin