抵抗素基因与肿瘤坏死因子α和白细胞在代谢综合征中的交互作用研究

Interactions between resistin gene and TNF-α and WBC in metabolic syndrome

目的探讨抵抗素(resistin)基因rs1862513、rs3219175、rs34124816、rs7408174、rs3745367位点多态性及其与血清肿瘤坏死因子α(TNF-α)、外周血白细胞(WBC)交互作用同代谢综合征(MS)间的关联。方法采用病例-对照研究设计,按照纳入排除标准,选择无血缘关系的376例MS患者为病例组,408例健康人为对照组。采用双抗体夹心酶联免疫吸附法(ELISA)测定血清中TNF-α的表达水平,运用Sequenom法检测抵抗素基因五位点多态性,使用SNPstats在线软件分析抵抗素基因各位点多态性与MS关系。采用Logistic回归分析、GMDR 0.7软件分别分析五位点与TNF-α、WBC间的交互作用。结果抵抗素基因五位点分别在不同遗传模型下的基因型分布,在MS组和对照组间的差异均无统计学意义(P>0.05)。Logistic回归分析显示,调整年龄、性别及民族后,TNF-α高水平与rs1862513位点CG或GG基因型、rs3219175位点GA基因型、rs34124816位点AC基因型、rs7408174位点TC或CC基因型、rs3745367位点GA或AA基因型间交互作用的OR值在2.930~10.506(P<0.05)。GMDR分析显示,由五位点与TNF-α组成的2~6因子交互作用模型分别与MS显著相关(均P<0.001),五位点与WBC组成的3~6因子交互作用模型也均与MS相关(均P<0.05或0.001),其中六因子模型均为最佳交互作用模型,交叉验证一致性(CVC)均为10/10,训练平衡准确度最高,发病风险最高。结论抵抗素基因rs1862513、rs3219175、rs34124816、rs7408174、rs3745367位点多态性可能与宁夏人群MS的患病无明显关联。五位点与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 resistin rs1862513,rs3219175,rs34124816,rs7408174,and rs3745367 gene polymorphisms,and their interactions with serum tumor necrosis factorα(TNF-α),white blood cell(WBC)and metabolic syndrome(MS).Methods Using the method of case-control study and according to inclusion and exclusion criteria,376 unrelated patients with MS were selected as the case group while another 408 healthy persons served as the control one.The expression of TNF-αin serum was determined by double antibody sandwich enzyme-linked immunosorbent assay(ELISA).The five-site polymorphism of resistin genes was detected by sequenom method.The relationships between the polymorphism of resistin genes and MS was analyzed by snpstats online software.Logistic regression analysis and GMDR0.7 software were used to analyze the interactions of the five sites with TNF-αand WBC.Results There was no significant difference in genotype distribution of the five sites of resistin genes between the MS group and control group in different genetic models(all P>0.05).Logistic regression analysis showed that after adjustment of age,sex and ethnicity,the OR value of interactions between high TNF-αlevel and CG or GG genotype of rs1862513 locus,GA genotype of rs3219175 locus,AC genotype of rs34124816 locus,TC or CC genotype of rs7408174 locus,GA or AA genotype of rs3745367 locus was 2.930-10.506(all P<0.05 or 0.01).GMDR analysis showed that the two-,three-,four-,five-,and six-factor interaction models consisting of five sites and TNF-αwere significantly associated with MS(both P<0.001),and the three-,four-,five-,and six-factor interaction models composed of five sites and WBC were also related to MS(both P<0.05 or 0.001).The six-factor model was the best one,whose cross-validation consistency(CVC)was 10/10,and the accuracy of training balance was the highest,suggesting that the risk of disease was the highest.Conclusion The polymorphisms of resistin gene rs1862513,rs3219175,rs34124816,rs7408174 and rs3745367 loci may not be associated with MS in Ningxia populations.The interactions between the five sites of resistin genes and TNF-αor WBC levels can significantly increase the risk of MS.