Objective: It is a known fact that Prodynorphin (PDYN) binds to kappa-opioid receptors and regulate dopaminergic tone, making this system important for the reinforcing and rewarding properties of drugs of abuse such as heroin, cocaine, and last but not least alcohol . The present study’s purpose was to evaluate potential association between alcohol dependence and four single nucleotide polymorphisms (SNPs) of PDYN gene (rs35286281 in promoter region and rs1022563, rs2235749, rs910080 in 3’UTR) among Turkish men.
Method: The Ethical Committee of the University approved the study and then the study was conducted with alcohol dependents (n=68, %43.3) at Bakirkoy Training and Research Hospital for Psychiatry, Neurology and Neurosurgery, Alcohol and Drug Research, Treatment and Training Center (AMATEM). Voluntary Turkish healthy control group (n=89, %56.7) was included in the study by Turgut Ozal University Faculty of Medicine Department of Psychiatry. The peripheral blood samples were obtained from patients and healthy controls were collected in EDTA coated tubes and 25 µl PCR mixture was prepared for amplification from the DNA samples. Genomic DNA was extracted from samples using a DNA isolation kit (Qiagen: Puregene Blood Core Kit B) according to the manufacturer’s instructions and then stored at -20°C until polymerase chain reaction (PCR) was performed. The genotypic analysis of the PDYN gene polymorphisms were performed using PCR-RFLP, whereas only PCR was used for VNTRs on PDYN gene. Sociodemographic features, Genotype and allele frequencies and difference between two groups were analyzed by Chi-square.
Results: Smoking cigarette, suicidal attempts, self-harming behavior, prison and police station experience were higher in alcohol dependence group. Moreover, there was a significant frequency of the PDYN 68bp VNTR (rs35286281) Genotype and allele frequencies in between two groups, but statistical significance of PDYN polymorphism 68bp VNTR (1022563) Genotype (p=0.053) and allele (p=0.057) frequencies are the limit. However, the PDYN 68bp VNTR (rs2235749 and rs910080) Genotype and allele frequencies did not differ between the groups.
Conclusion: The present study’s main finding is a significant higher frequency of the PDYN 68bp VNTR (rs35286281) L allele in alcohol-dependent subjects than in controls. Previous studies that have examined the relationship between PDYN polymorphism and substance use disorders (SUDs) but results are controversial, with some studies showing that high PDYN expressing alleles are more common among people with SUDs, some showing low expression alleles in association with SUDs and others reporting no association. The inconsistent results across studies can be attributed to a variety of factors such as sample sizes, ethnic diversity, culture, drug availability, legislation and the examination of different SUDs or alcohol dependence since gene polymorphisms is not the only etiological factor for addiction. Thus, further research is required.