Boroumand Fariba, Mahmoudinasab Hamideh, Saadat Mostafa
Department of Biology, College of Sciences, Shiraz University, Shiraz 71467-13565, Iran.
Department of Biology, College of Sciences, Shiraz University, Shiraz 71467-13565, Iran.
Gene. 2018 Apr 5;649:27-31. doi: 10.1016/j.gene.2018.01.074. Epub 2018 Feb 6.
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.
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.
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.
The rs2758339 and rs5746136 polymorphisms of the SOD2 are associated with the risk of HD but not associated with the SOD2 expression level.
超氧化物歧化酶2（SOD2，在线人类孟德尔遗传数据库编号：147460）参与超氧阴离子的解毒过程。在暴露于吗啡的细胞中，SOD2信使核糖核酸水平下调。氧化应激在药物依赖中起重要作用。rs2758339（A/C）位于SP1和核因子κB转录元件序列附近，rs5746136（A/G）产生一个新的糖皮质激素受体结合位点。综合来看，推测这些多态性可能与海洛因依赖（HD）风险及SOD2表达水平相关。
为研究SOD2多态性与HD风险之间的关联，纳入了442名海洛因依赖者和799名健康对照者。本研究还包括77名设拉子大学（伊朗）的健康学生，以研究SOD2多态性与基因表达水平之间的关联。
rs2758339的AC（比值比[OR] = 0.72，95%可信区间[CI] = 0.56 - 0.93，P = 0.013）和CC（OR = 0.64，95% CI = 0.45 - 0.92，P = 0.015）基因型与HD风险呈负相关。rs5746136的AA基因型增加了HD风险（OR = 1.46，95% CI = 1.03 - 2.07，P = 0.031）。AA单倍型与HD风险相关（OR = 1.31，95% CI = 1.09 - 1.58，P = 0.004）。研究的基因型（或双倍型）与SOD2表达水平之间无关联。
SOD2的rs2758339和rs5746136多态性与HD风险相关，但与SOD2表达水平无关。
