Association of the SOD2 (rs2758339 and rs5746136) polymorphisms with the risk of heroin dependency and the SOD2 expression levels

Abstract

Background: Superoxide dismutase-2 (SOD2, OMIM: 147460) is involved in the detoxification of superoxide anions. The SOD2 mRNA level is down-regulated in cells exposed to morphine. Oxidative stress plays an important role in drug dependency. The rs2758339 (A/C) is located in the vicinity of SP1 and NF-κB transcription element sequences and the rs5746136 (A/G) creates a new glucocorticoid receptor binding site. Taken together, it is hypothesized that these polymorphisms might be associated with the risk of heroin dependency (HD) and the SOD2 expression level.

Methods: To investigate the association between the SOD2 polymorphisms and the risk of HD, 442 heroin dependent persons and 799 healthy controls were included. This study also, consisted of 77 healthy students of Shiraz University (Iran) to investigate the association between the SOD2 polymorphisms and the gene expression level.

Results: The AC (OR = 0.72, 95% CI = 0.56-0.93, P = 0.013) and CC (OR = 0.64, 95% CI = 0.45-0.92, P = 0.015) genotypes of the rs2758339 were negatively associated with the risk of HD. The AA genotype of the rs5746136 increased the risk of HD (OR = 1.46, 95% CI = 1.03-2.07, P = 0.031). The AA haplotype was associated with the risk of HD (OR = 1.31, 95% CI = 1.09-1.58, P = 0.004). There was no relationship between the study genotypes (or diplotypes) and the SOD2 expression level.

Conclusion: The rs2758339 and rs5746136 polymorphisms of the SOD2 are associated with the risk of HD but not associated with the SOD2 expression level.

Keywords: Heroin dependency; SOD2; mRNA level; rs2758339; rs5746136.