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.