Background:Many studies have suggested that cigarette smoking and polymorphisms ofresistin and glutathione peroxidase-1 (GPx-1) genes are closely correlated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD).However,few reports have investigated these associations with respect to NAFLD susceptibility.We,therefore,examined the distribution ofpolymorphisms in GPx-1 and resistin genes in NAFLD patients and healthy controls and analyzed the relationship between these polymorphisms and smoking status.Methods:Nine hundred NAFLD patients and 900 healthy controls were selected,and the genetic polymorphisms of resistin gene promoter-420C/G and GPx-1 gene Pro 198Leu were analyzed by polymorphism-polymerase chain reaction (PCR) in DNA extracted from peripheral blood leukocytes.Interactions between the two mutants and the gene-environment interaction with cigarette smoking were also analyzed.Results:Genotype frequencies of-420C/G (GG) and Pro198Leu (LL) were significantly higher in NAFLD cases (49.56％ and 50.11％,respectively) compared with healthy controls (23.67％ and 24.22％,respectively) (P =0.0069; P =0.0072).Moreover,the risk of NAFLD with-420C/G (GG) was significantly higher than in controls (odds ratio [OR] =3.1685,95％ confidence interval (CI) =1.9366-5.2073).Individuals carrying Pro198Leu (LL) had a high risk of NAFLD (OR =3.1424,95％ CI =1.7951-5.2367).Combined analysis of the polymorphisms showed that the-420C/G (GG)/Pro198Leu (LL) genotype was significantly more common in the NAFLD group than in the control group (39.44％ vs.12.78％,respectively,P =0.0054),while individuals with-420C/G (GG)/Pro198Leu (LL) had a high risk of NAFLD (OR =5.0357,95％ CI =3.1852-7.8106).Moreover,the cigarette smoking rate in the NAFLD group was significantly higher than in the control group (OR =1.8990,P =0.0083 in the smoking index (SI) ≤400 subgroup; OR =5.0937,P =0.0051 in the SI ＞400 subgroup),and statistical analysis suggested a positive interaction between cigarette smoking and-420C/G (GG) (γ =5.6018 in the SI ≤400 subgroup; γ=4.4770 in the SI ＞400 subgroup) and Pro198Leu (LL) (γ =5.7715 in the SI ≤400 subgroup; γ =4.5985 in the SI ＞400 subgroup) in increasing the risk of NAFLD.Conclusion:NAFLD risk factors include-420C/G (GG),Pro 198Leu (LL) and cigarette smoking,and these three factors have a significant additive effect on NAFLD risk.