IL-6基因与TNF-α和WBC在代谢综合征中的交互作用

Interaction of IL-6 gene with tumor necrosis factor-α and white blood cell in metabolic syndrome

目的探讨白细胞介素6(interleukin 6,IL-6)基因-634C/G、-174G/C、-1363G/T位点多态性及交互作用以及与血清肿瘤坏死因子(tumor necrosis factor,TNF-α),外周血白细胞(white blood cell,WBC)交互作用与代谢综合征(metabolicsyndrome,MS)间的关联。方法﹑运用病例-对照的研究方法,按照纳入与排除标准,于2015年3月到2016年3月从宁夏医科大学总医院及吴忠市人民医院,选取无血缘关系的376例病例组和408例对照组,问卷调查一般情况,疾病及用药史、家族史等,测量身高、体重、腰围、臀围、收缩压、舒张压等,并计算体质指数(body massindex,BMI)及腰臀比(waist-to-hip ratio,WHR),采集血液并检测白细胞计数、血糖、血清、TNF-α,甘油三酯﹑总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇等水平,进行IL-6基因-634C/G、-174G/C、-1363G/T位点多态性检测。使用SNPstats在线软件分析抵抗素基因各位点多态性与MS关系。运用SHEsis在线软件分析IL-6基因3位点连锁不平衡及单体型与MS的关系。采用GMDR 0.7软件分析IL-6基因3位点与TNF-α,WBC间的交互作用。结果﹐调整性别﹑年龄前后,IL-6基因3位点多态性在不同遗传模型下与MS的发病无关(P>0.05)。IL-6基因3位点间存在连锁不平衡,但这3位点构成的单倍体与MS的易感性无关联(P>0.05)。3位点间不存在交互作用,但3位点与TNF-α组成的二因子、三因子、四因子交互作用模型均P<0.001,置换检验均P<0.001,差异均有统计学意义,与MS的发病有关;三位点与WBC组成的二因子、三因子,四因子交互作用模型均P<0.05,置换检验均P<0.05。结论IL-6基因-634C/G、-174G/C、-1363G/T位点多态性可能与MS的患病无明显关联。3位点与TNF-α,WBC水平存在交互作用,可使MS的患病风险显著增高。

OBJECTIVE To investigate the associations between the polymorphisms and interaction of the interleukin 6(IL-6) genes at-634 C/G,-174 G/C,-1363 G/T loci, as well as the interactions between the three loci and tumor necrosis factor(TNF-α), and peripheral blood leukocytes(white blood cell, WBC) with metabolic syndrome(MS). METHODS Using the case-control research method, according to the inclusion and exclusion criteria, from March 2015 to March 2016 from the General Hospital of Ningxia Medical University and Wuzhong City People’s Hospital, 376 unrelated cases and 408 control groups were selected. We conducted questionnaire surveys(including general conditions, disease and medication history, family history, etc.), physical examinations(including height, weight and calculation of body mass index(BMI), waist circumference, hip circumference and calculation of waist-to-hip ratio(WHR), SBP, DBP, etc.), blood collection and testing(including WBC count, serum TNF-α level and biochemical indicators TG, TC, HDL-C, LDL-C, FPG, UA, AST, ALT, etc.), and the polymorphism detection of IL-6 gene at-634 C/G,-174 G/C,-1363 G/T sites.The SNPstats online software was used to analyze the relationship between the polymorphisms of IL-6 gene and MS. The SHEsis online software was used to analyze the linkage disequilibrium(LD) of the IL-6 three-site and the relationship between haplotype and MS. GMDR 0.7 software was used to analyze the interactions among the three sites of IL-6 gene, and one between the three sites and TNF-α and WBC, respectively. RESULTS Before and after adjustment of sex, age and nationality, the polymorphism at the 3 position of IL-6 gene was not related to the onset of MS in different genetic models(both P> 0.05). There was a linkage disequilibrium between the three loci of IL-6 gene, but the haploids formed by these three loci were not associated with MS susceptibility(all P> 0.05). There was no interaction among the three sites, but the two-factor, three-factor, and four-factor interaction models consisting of the three sites and TNF-α were all statistically significant(all P<0.001) and the replacement tests were all P<0.001, and were all associated with MS occurrence. The two-factor, three-factor, and four-factor interaction models consisting of the three sites and WBC were all P<0.01, and the replacement tests were all P<0.05. The differences were statistically significant, which was related to the onset of MS. CONCLUSION The IL-6 gene-634 C/G,-174 G/C, and-1363 G/T loci polymorphism may not be significantly associated with the prevalence of MS. Interactions between the three sites and TNF-α and WBC levels can significantly increase the risk of MS.