IN VITRO AND IN SILICO STUDIES OF A118G MISSENSE MUTATION IN ASSOCIATION WITH OPIOID ADDICTION AMONG NORTHERN IRANIANS UNDERWENT METHADONE TREATMENT

Background and Aim : Abundant studies have reported the associations of OPRM1 gene as one the most important archaic genes with various addictions, and rs1799971 (A118) as a Single Nucleotide Polymorphism (SNP) has represented splendid impacts on the OPRM1 functions and regulations. This study investigated the association of A118G with opioid addiction among Iranians and in silico analyses were performed regarding personalized medicine.Methods : 404 addicted men were genotyped with Amplification Refractory Mutation System (ARMS) PCR. In silico studies were designed through homology modeling of dominant (A118: N40) and recessive (G118: D40) structures and docked them with 41 FDA-approved drugs of OPRM1 protein by SWISS-MODEL, COACH, Molprobity, ProSA, Errat, Glide XP, and Autodock 4. Also, the regulatory role of A118G was assessed with TFBind.Results : Results showed that A118G was significantly associated with opioid addiction under a dominant model of inheritance (P=0.017). Docking results revealed the higher binding affinity of N40 rather than D40 model; however, methadone and morphine were bonded with D40 model more powerful than N40. Also, the recessive allele of A118G in the promoter of OPRM1 indicated a lack of binding to MYB and CETS1P53 transcription factors compared with dominant allele (A).Conclusion : Consequently, A118G showed significant association with susceptibility to opioid addiction among Iranians and based on its both structural and regulatory roles, it might be the most potential SNP marker of OPRM1 gene for diagnosis and treatment of opioid addiction

Keywords:

OPRM1 , opioid addiction , homology modeling , molecular docking.