engleski

OPRM1 gene polymorphism and addiction to smoking in patients with schizophrenia

Various evidence suggests that in people with certain neuropsychiatric disorders, such as schizophrenia, the incidence of smoking is significantly higher than in healthy individuals, which is usually explained by the attempt of patients to alleviate the presence of psychiatric symptoms and emotional stress. On the other hand, studies suggest the involvement of the opioid system in the development of schizophrenia and drug addiction, including addiction to nicotine. In the gene OPRM1 encoding the μ opioid receptor type 1, more than 250 different polymorphisms have been found. The rs1799971 polymorphism (A118G) in the OPRM1 gene has been associated with the development of addiction to heroin, amphetamine, nicotine, and alcohol. This polymorphism results in the replacement of amino acids (Asn40Asp), and consequently changes the expression of the receptor and its affinity for the endogenous opioids. The polymorphism rs510769 is also associated with the risk of developing addictions to heroin and amphetamine. Since this polymorphism is located in the intronic region, it is assumed that it could change the function of the OPRM1gene by influencing the alternative intron splicing. To further investigate the role of the gene coding for the μ opioid receptor type 1 in nicotine dependence and schizophrenia, the aim of this research was to investigate the possible associations of polymorphisms rs1799971 and rs510769, in the OPRM1 gene, with smoking in schizophrenic patients. The proposed study involved 204 subjects of Croatian origin, both sexes (64 males and 140 females) with schizophrenia. Of the total number of respondents, 142 were smokers and 62 non- smokers. DNA samples extracted from the blood of all patients by Miller's isolation method were subjected to the genotyping of rs510769 and rs1799971 polymorphisms in the OPRM1 gene. The significance of deviations from the genotype distribution, as well as the differences in the distribution of genotypes, alleles and carrier polymorphisms rs1799971 and rs510769 located in the OPRM1 gene, were determined by using the χ2 test or Fisher test. The program «Haploview version 4.2» was used to construct LD matrix and determine the haplotype block of rs1799971 and rs510769 polymorphisms. Statistically significant differences were considered when the probability p was less than 0.05. The results of our research showed association between rs1799971 polymorphism in the OPRM1 gene and smoking in schizophrenic patients. Although these results have not been confirmed for the rs510769 polymorphism, the haplotypic association with smoking in subjects with schizophrenia has been found for combination of rs1799971 and rs510769 polymorphisms. Future aims are to determine the possible association of rs1799971 and rs510769 polymorphisms with smoking in healthy controls to see if these polymorphisms are associated with smoking just in schizophrenic patients or with smoking in general.

OPRM1 ; Polymorphism ; Smoking ; Schizophrenia

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