Association Study Between Single Nucleotide Polymorphisms In Exon1, 5' Regulatory Region Of μ Opioid Receptor Gene And Heroin Dependence

Objective:To investigate the association of single nucleotide polymorphisms(SNPs)in exonl, 5′regulatory region ofμopioid receptor gene(OPRM1) andsusceptibility of heroin dependence, clinical features and combinationof other drug abuse.Methods:A case-control study was designed by collecting the blood sample of 170heroin addicts and 124 health controls who are Han nationalities inYunnan province, and detecting -2044C/A, -1793T/A, 17C/T and 118A/Gpolymorphisms by Polymerase Chain Reaction-Restriction Fragment Lengthpolymorphisms (PCR-RFLP) technique. The clinical features and statusof drug use were collecting by Diagnostic Interview for Genetic Studies,Rating Scale for Prolonged Withdrawal Symptoms of Heroin and aself-developed questionnaire to analyze the association of clinicalphenotype and genotypes/alleles. Results:1. Alleles OPRM1-2044A,-1793A and 17T are very rare in the objects ofthis study. There is only 1 Heterozygote -2044CA in case group.Alleles-1793A andd17T do not be found in all objects.2. There were no statistical significances in distribution of genotypebetween cases and controls(P=0.092), but the frequency of alleleOPRMI 118G is significantly higher in these patients than incontrols(P=0.035). Also, the frequency of allele OPRM1 118G issignificantly higher in male patients than in male controls(P=0.041), but not in female patients than in female controls. The samedeference has been found in the male who carry the 118G or not betweencases and controls (P=0.031), but not in female.3. The differences among many clinical feathers and genotypes do notbe observed in heroin addicts (P>0.05), including the age of firstattempting heroin, the time to be addict, heroin intake dosages,craving level, prolonged withdrawal symptoms and duration, even ifthe genotype has been evaluated by 3 methods. But high or euphoricfeeling has significant difference among heroin addicts withdifferent genotype (P=0.016), and individuals who carry allele 118Acould feel higher euphoria than ones who not carry.4. The distribution of heroin addicts who have combination of heroindependence and other drug abuse or not has not significant differenceamong genotypes, and genotype also has been evaluated by 3 methods.But the significant difference among genotypes has been found betweenindividuals combined of heroin dependence and alcohol dependence ornot (P=0.035), and proportion of allele G carriers who havecombination dependence of alcohol is significantly higher than ofindividual without allele G. Conclusions:1. OPRM1 118A/G polymorphism may be associated with the vulnerabilityof heroin dependence in male Han nationality of Yunnan, the variantG allele may contribute to the morbidity.2. The genotype and allete of OPRM1 118A/G polymorphism may have notassociation to the age of first attempting heroin, the time to beaddict, heroin intake dosages, craving level, prolonged withdrawalsymptoms and duration among Han heroin addicts in Yunnan. The addictscarrying 118A allele may have higher euphoric felling than them whonot carrying.3. The 118G allele carriers may be more vulnerably to the combinationof alcohol in male heroin addicts of Han nationality in Yunnan.4. The frequencies of OPRM1-2044A, -1793A and 17T allele is very lowin the subjects, so OPRM1-2044,-1793, 17T locus may have not singlenucleotide polymorphisms in Yunnan Han population.