XRCC4 rs6869366 polymorphism is associated with susceptibility to both nicotine dependence and/or schizophrenia

Abstract Background: Oxidative stress induced DNA damage has been assumed to contribute to the etiopathogenesis of schizophrenia (Sch). Smoking prevalence was more common in patients with Sch. The X-ray repair cross-complementation group 4 (XRCC4) gene plays an important role in the repair of DNA double-strand breaks. Objective: The purpose of this study was to investigate whether XRCC4 rs6869366 polymorphism has a relationship both in nicotine dependence (ND) and Sch+ND risk. Methods: One hundred and four patients with Sch+ND, 133 subjects with ND only and 70 healthy controls were enrolled in the study. XRCC4 rs6869366 polymorphism was analyzed using PCR-RFLP assay. Results: The frequency of XRCC4 rs6869366 GG genotype was more common in the ND and Sch+ND group than controls (p = 0.001 and p = 0.001, respectively). XRCC4 rs6869366 TT genotype was lower in both ND and Sch+ND group compared to controls (p = 0.001 and p = 0.001, respectively). Also, XRCC4 rs6869366 G allele was higher in Sch+ND group than controls (p = 0.001) while XRCC4 rs6869366 T allele was lower in ND group than healthy controls (p=0.001). XRCC4 rs6869366 GT genotype was lower in ND group than control group (p = 0.003). Discussion: These results suggested that the XRCC4 rs6869366 polymorphism G related genotype/allele was associated with susceptibility to both ND and Sch+ND in a Turkish population.

摘要
背景：氧化应激诱导的DNA损伤被认为与精神分裂症（schizophrenia, Sch）的发病机制相关。精神分裂症患者的吸烟患病率更高。X射线修复交叉互补基因4（X-ray repair cross-complementation group 4, XRCC4）在DNA双链断裂修复中发挥重要作用。
目的：本研究旨在探讨XRCC4 rs6869366多态性是否与尼古丁依赖（nicotine dependence, ND）及精神分裂症伴尼古丁依赖（Sch+ND）的发病风险存在关联。
方法：本研究共纳入104例Sch+ND患者、133例单纯尼古丁依赖受试者及70名健康对照者。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析法对XRCC4 rs6869366多态性进行检测。
结果：ND组及Sch+ND组的XRCC4 rs6869366 GG基因型频率均高于健康对照组（分别为p=0.001及p=0.001）；ND组与Sch+ND组的TT基因型频率均低于健康对照组（分别为p=0.001及p=0.001）。此外，Sch+ND组的XRCC4 rs6869366 G等位基因频率高于健康对照组（p=0.001），而ND组的T等位基因频率低于健康对照组（p=0.001）。同时，ND组的XRCC4 rs6869366 GT基因型频率低于健康对照组（p=0.003）。
讨论：本研究结果表明，在土耳其人群中，XRCC4 rs6869366多态性的G相关基因型/等位基因与尼古丁依赖及精神分裂症伴尼古丁依赖的易感性相关。