Interaction of Polymorphisms of Resistin Gene Promoter -420C/G, Glutathione Peroxidase -1 Gene Pro198Leu and Cigarette Smoking in Nonalcoholic Fatty Liver Disease

Background： Many studies have suggested that cigarette smoking and polymorphisms of resi stin and glutathione peroxidase-1 （GPx-1） genes are closely correlated with tile pathogenesis of nonalcoholic lhtty liver disease （NAFLD）. However, few reports have investigated these associations with respect to NAFLD susceptibility. We, therefore, exalnined the distribution of polymorphisms in GPx-l 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 tile 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 （GGJ was significantly higher than in controls （odds ratio [OR] =3.1685, 95% confidence interval （（7） 1.9366-5.2073）. Individuals carrying Pro198Leu （LL） had a high risk of NAFLD （OR - 3.1424, 95% C/= 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.（1357, 95% CI= 3.1852 7.8106）. Moreover, the cigarette smoking rate in the NAFLD group was significantly higher than in tile 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） （y = 5.6018 in tile SI≤400 subgroup; γ - 4.4770 in the SI 〉400 subgroup） and Pro198Leu （LL） （y = 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）, Pro198Leu （LL） and cigarette smoking, and these three factors have a significant additive effect on NAFLD risk.