Haplotype-based association study of Opioid Receptor Kappa-type ۱ (OPRK۱) gene polymorphisms with nicotine dependence

Background and Aim: Meta-analyses and twins studies have reported that personal behaviors in tobacco use, vulnerability to dependence, and the ability to quit smoking, are associated with single nucleotide polymorphisms (SNPs). Opioid Receptor Kappa-type ۱ (OPRK۱) is one of the key genes in the opioid pathway. The present study aimed to find the plausible associations of OPRK۱ SNPs including rs۹۹۷۹۱۷, rs۶۹۸۵۶۰۶, and rs۶۴۷۳۷۹۷ with susceptibility to nicotine dependence (ND).Methods: DNA from ۴۰۴ samples (۲۰۲ smokers and ۲۰۲ healthy people) were extracted by salting-out standard technique, and then genotyped through Amplification Refractory Mutation System (ARMS) PCR. All statistical analyses were done by SNPAlyze version ۸.۱ and SPSS version ۲۰.Results: Data showed that two SNPs (rs۹۹۷۹۱۷ and rs۶۹۸۵۶۰۶) had significant associations with ND both under a recessive model of inheritance (P=۴.۲۲E-۶ and P=۱.۵۸E-۷, respectively). Moreover, there were four haplotypes with an overall frequency higher than ۰.۰۵, with significant associations with ND including C-T-C (Permutation P (PP)=۰.۰۰۱), C-T-T (PP<۰.۰۰۰۱), C-C-T (PP= ۰.۰۰۸), and T-T-C (PP<۰.۰۰۰۱). Linkage Disequilibrium (LD) analyses showed no significant association neither in r-square no in D’-value.Conclusion: Conclusively, SNPs of OPRK۱ might have remarkable roles with ND among Iranians and also valuable for gene-gene interactions in further studies to design better strategies in personalized medicine.

Keywords:

Association , nicotine dependence , OPRK۱ , SNP , haplotype.