文章摘要
吴鹏波,舒泳翔,李明,罗和生,张国,谭诗云.间质金属蛋白酶基因多态性与中心性肥胖在非酒精性脂肪肝病中交互作用研究[J].中华流行病学杂志,2015,36(12):1415-1418
间质金属蛋白酶基因多态性与中心性肥胖在非酒精性脂肪肝病中交互作用研究
Study on the interaction between matrix metalloproteinases gene polymorphism and central obesity in nonalcoholic fatty liver disease
收稿日期:2015-04-30  出版日期:2015-12-15
DOI:10.3760/cma.j.issn.0254-6450.2015.12.022
中文关键词: 基质金属蛋白酶;非酒精性脂肪肝病;多态性;中心性肥胖;交互作用
英文关键词: Matrix metalloproteinases;Nonalcoholic fatty liver disease;Polymorphism;Central obesity;Interaction
基金项目:湖北省自然基金项目(2012CDZ029)
作者单位E-mail
吴鹏波 430060 武汉大学人民医院消化内科  
舒泳翔 430060 武汉大学人民医院消化内科  
李明 430060 武汉大学人民医院消化内科  
罗和生 430060 武汉大学人民医院消化内科  
张国 广西壮族自治区人民医院消化内科  
谭诗云 430060 武汉大学人民医院消化内科 tanshiyun@medmail.com 
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中文摘要:
      目的 探讨间质金属蛋白酶-9(MMP-9)-1562C/T(rs3918242)以及MMP-2-1306C/T(rs243865)位点单核苷酸多态性(SNP)与非酒精性脂肪肝(NAFLD)遗传易感性以及与中心性肥胖交互作用。方法 对545例NAFLD患者和636例正常对照,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析rs24386以及rs3918242基因型、非条件logistic分析各基因型与脂肪肝发病易感性关系,利用非条件logistic分析和广义多因子降维(GMDR)法分析rs3918242、rs243865与中心性肥胖的交互作用。结果 MMP-9 rs3918242位点T基因携带者(TT/CT)与非T基因携带者(CC)的NAFLD罹患风险明显增加(OR=1.67,95%CI:1.32~2.12,P=0.001;调整OR=1.65,95%CI:1.31~2.01,P=0.008);而MMP-2 rs243865位点T基因携带者(TT/CT)与非T基因携带者(CC)的NAFLD罹患风险明显降低(OR=0.68,95%CI:0.53~0.86,P=0.001;调整OR=0.66,95%CI:0.49~0.90,P=0.007)。广义多因子降维法分析结果显示,rs3918242与中心性肥胖在NAFLD发病中存在交互作用(P=0.001)。利用非条件logistic校正年龄、性别、腰围、BMI、LDL-C、HDL-C、FPG、胰岛素抵抗指数后,分析显示,携带rs3918242 TT/CT基因型中心性肥胖个体罹患NAFLD的风险高于携带CC基因非吸烟个体(OR=4.50,95%CI:2.78~7.17,P=0.007)。结论 MMP-9基因的rs3918242以及MMP-2基因的rs243865与NAFLD患病罹患风险紧密相关,rs3918242与中心性肥胖在NAFLD发病中具有协同效应。
英文摘要:
      Objective To study whether matrix metalloproteinases-9(MMP)-1562C/T(rs3918242) and MMP-2-1306C/T (rs243865) were associated with the susceptibility on nonalcoholic fatty liver disease (NAFLD) and the interactions between the two factors and central obesity. Methods Genotypes of 545 patients and 636 subjects with NAFLD under control were examined by polymerase chain reaction-based restriction fragment length polymorphism(PCR-RFLP). Unconditional logistic regression (ULR) was performed to assess the NAFLD risk. The gene-environment interactions on the risk of NAFLD were explored by generalized multifactor dimensionality reduction (GMDR) and ULR methods. Results Results from the case-control analysis indicated that there was an increased risk of developing NAFLD for MMP-9 rs3918242 (TT/CT) genotype carriers, when compared with the non-carriers (CC), with OR=1.67,95%CI: 1.32-2.12, P=0.001; Adjusted OR=1.65,95%CI:1.31-2.01(P=0.008). However, risk reduction of NAFLD was found when MMP-2 rs243865 (TT/CT) genotype carriers compared with the non-carriers (CC), with OR=0.68, 95%CI:0.53-0.86,P=0.001; with adjusted OR=0.66, 95%CI: 0.49-0.90(P=0.007). Data from the GMDR showed that gene-environment interaction among rs3918242 and central obesity on the risk of NAFLD might be significant (P=0.001). By using the ULR method, subjects as central obesity-positive but with genotype CT/TT, appeared having 4.50 (95%CI:2.78-7.17,P=0.007) times risk of NAFLD, when compared to the central obesity-negative subjects with genotype CC after adjusting for the covariates. Conclusion MMP-9 rs3918242, MMP-2 rs243865 were associated with risk of NAFLD while both rs3918242 and central obesity showing synergistic effects on the risk of the NAFLD.
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