Interactions of central obesity with rs3918242 on risk of non-alcoholic fat liver disease: a preliminary case-control study.

NAFLD is a complex disease characterized by inflammation and insulin resistance which is determined by an interaction of genetics and environmental factors. MMP gene has been implicated in relation to inflammation and insulin resistance. The preliminary case-control study aimed to investigate the association between Matrix metalloproteinase (MMP)-9-1562C/T (rs3918242), MMP-2-1306C/T (rs243865) and risk of NAFLD and to further evaluate the interactions of central obesity with rs3918242 and rs243865. Two variants, rs3918242 and rs243865, were genotyped by polymerase chain reaction -restriction fragment length polymorphism. Gene-environment interactions on risk of NAFLD was preliminarily investigated by generalized multifactor dimensionality reduction (GMDR) and further confirmed by unconditional logistic regression methods. After adjusting for covariates, increased risk of NAFLD were observed in subjects carrying TT/CT genotypes in rs3918242 ((Adjust)OR=1.64, 95% CI: 1.24, 2.11, P=0.006). However, decreased risk of non-alcoholic fat liver disease was found when MMP-2 rs243865 (TT/CT) genotype carriers compared with CC carrier ((Adjust)OR=0.65, 95% CI: 0.47, 0.72, P=0.000).Interactions of central obesity with rs3918242 was preliminarily found by GMDR, with a maximum prediction accuracy (67.61%) and a maximum Cross-validation Consistency (10/10).The unconditional logistic regression method indicated central obesity-positive subject with genotype TT/CT had 4.54 times risk of NAFLD compared to central obesity-negative subjects with genotype CC (OR(add)(a)=4.54, 95% CI: 2.81, 7.21, P(add)(a)=0.000), which further confirmed the interactions. The results indicate that both rs3918242 and rs243865 is associated with risk of NAFLD. Furthermore, rs3918242 and central obesity have synergistic effects on risk of NAFLD.

Interactions of smoking with rs833061 polymorphism on the risk of non-alcoholic fat liver disease in Hubei Han population: a preliminary case-control study.

OBJECTIVES: Vascular endothelial growth factor (VEGF) has biological actions on energy homeostasis, inflammation and insulin resistance. The present study aimed to investigate the association between VEGF -460 T/C (rs833061), and +936 C/T (rs3025039) polymorphism and risk of non-alcohol fatty liver disease (NAFLD) in Hubei Han population and to further explore the interactions of smoking with rs833061 and rs3025039. MATERIALS AND METHODS: 341 healthy controls and 246 cases were recruited. Two variants, rs833061 and rs3025039, were genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). The unconditional logistic regression (ULR) was performed to assess the association of the two variants with risk of NAFLD. Gene-environment interactions on the risk of NAFLD were preliminarily explored by generalized multifactor dimensionality reduction (GMDR) and further confirmed by ULR methods. RESULTS: After adjusting for covariates, increased risk of NAFLD was observed in patients carrying CT/CC genotypes in rs833061 and rs3025039 (ORa=1.80, 95% confidence interval (CI): 1.51, 2.36, Pa =0.000; ORa=1.89, 95% CI: 1.41, 2.82, Pa =0.000, respectively). Interaction of smoking with rs833061 was found by GMDR, with maximum prediction accuracy (67.91%) and a maximum cross-validation consistency (10/10). ULR method confirmed that, smoking-positive patients with genotype CT/CC had 4.93 times risk of NAFLD compared to smoking-negative participants with genotype TT (ORadd (a)=4.93, 95% CI: 2.91, 8.54, P add (a)=0.000), which further confirmed synergistic effects. CONCLUSION: The results indicated that both rs833061 and rs3025039 are associated with NAFLD risk. Furthermore, rs833061 is likely to have an interaction with smoking, and they have synergistic effects on risk of NAFLD in Hubei Han population.