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[基质金属蛋白酶基因多态性与非酒精性脂肪性肝病中心性肥胖的相互作用研究]

[Study on the interaction between matrix metalloproteinases gene polymorphism and central obesity in nonalcoholic fatty liver disease].

作者信息

Wu Pengbo, Shu Yongxiang, Li Ming, Luo Hesheng, Zhang Guo, Tan Shiyun

机构信息

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, China.

Department of Gastroenterology, the People's Hospital of Guangxi Zhuang Autonomous Region.

出版信息

Zhonghua Liu Xing Bing Xue Za Zhi. 2015 Dec;36(12):1415-8.

PMID:26850403
Abstract

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.

摘要

目的

研究基质金属蛋白酶-9(MMP)-1562C/T(rs3918242)和MMP-2-1306C/T(rs243865)是否与非酒精性脂肪性肝病(NAFLD)易感性相关,以及这两个因素与中心性肥胖之间的相互作用。

方法

采用基于聚合酶链反应的限制性片段长度多态性(PCR-RFLP)技术检测545例患者和636例对照受试者的基因型。采用非条件逻辑回归(ULR)评估NAFLD风险。通过广义多因素降维法(GMDR)和ULR方法探讨基因-环境相互作用对NAFLD风险的影响。

结果

病例对照分析结果显示,与非携带者(CC)相比,MMP-9 rs3918242(TT/CT)基因型携带者发生NAFLD的风险增加,OR=1.67,95%CI:1.32-2.12,P=0.001;调整后的OR=1.65,95%CI:1.31-2.01(P=0.008)。然而,与非携带者(CC)相比,MMP-2 rs243865(TT/CT)基因型携带者的NAFLD风险降低,OR=0.68,95%CI:0.53-0.86,P=0.001;调整后的OR=0.66,95%CI:0.49-0.90(P=从GMDR获得的数据显示,rs3918242与中心性肥胖之间的基因-环境相互作用对NAFLD风险可能具有显著意义(P=0.001)。采用ULR方法,在调整协变量后,中心性肥胖阳性但基因型为CT/TT的受试者发生NAFLD的风险是中心性肥胖阴性且基因型为CC的受试者的4.50倍(95%CI:2.78-7.17,P=0.007)。

结论

MMP-9 rs3918242、MMP-2 rs243865与NAFLD风险相关,而rs3918242和中心性肥胖均对NAFLD风险具有协同作用。 0.007)。

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