Interaction between Helicobacter pylori infection and polymorphisms of PPAR-γ2 gene Pro12Ala and GPx-1 gene Pro198Leu and its association with nonalcoholic fatty liver disease

Objective To investigate the interaction between Helicobacter pylori infection and polymorphisms of PPAR-γ2 gene Pro12 Ala and GPx-1 gene Pro198 Leu and its association with nonalcoholic fatty liver disease ( NAFLD) . Methods A total of 750 patients with nonalcoholic fatty liver ( NAFL) , 750 patients with nonalcoholic steatohepatitis ( NASH) , and 750 patients with nonalcoholic fatty hepatic cirrhosis ( NAFHC) who were treated or hospitalized in The First Affiliated Hospital of Xinxiang Medical University from March 2011 to July2015 were enrolled, and 750 individuals who underwent physical examination were enrolled as control group. Peripheral blood leukocytes were collected for each group, and PCR-RFLP was used to detect the polymorphisms of Pro12 Ala and Pro198 Leu. The14 C-urea breath test was used to measure disintegration per minute ( DPM) of Helicobacter pylori binding to14 C, in order to evaluate the degree of Helicobacter pylori infection. A face-to-face questionnaire survey was performed for each subject. The t-test was used for comparison of continuous data between two groups, the chi-square test was used for comparison of categorical data between groups. The multivariate logistic regression model was used for data analysis. The adjusted odds ratio ( OR) and 95% confidence interval of Pro12 Ala polymorphism, Pro198 Leu polymorphism, and Helicobacter pylori infection for the risk of NAFLD were calculated, and the interaction between Helicobacter pylori infection and polymorphism of PPAR-γ2 gene Pro12 Ala and GPx-1 gene Pro198 Leu was analyzed. Results The patients with the genotypes of Pro12 Ala ( PA) , Pro12 Ala ( AA) , Pro198 Leu ( PL) , and Pro198 Leu ( LL) had a significant increase in the risk of NAFLD ( OR = 5. 732 4, 5. 973 2, 6. 360 5, and 6. 165 7, all P < 0. 01) . The combined analysis of the polymorphisms showed positive interactions between Pro12 Ala ( PA) and Pro198 Leu ( PL) , between Pro12 Ala ( PA) and Pro198 Leu ( LL) , between Pro12 Ala ( AA) and Pro198 Leu ( PL) , and between Pro12 Ala ( AA) and Pro198 Leu ( LL) ( all γ > 1) . The Helicobacter pylori infection patients with 100≤DPM < 500 or DPM≥500 had a significant increase in the risk of NAFLD ( 100≤DPM < 500: ORNAFL= 2. 064 1, ORNASH= 4. 448 5, ORNAFHC= 10. 969 5;DPM≥500: ORNAFL= 3. 130 5, ORNASH= 8. 024 6, ORNAFHC= 21. 461 4) , and the patients with DPM≥500 had a significantly higher risk of NAFLD than those with 100 ≤ DPM < 500 ( P < 0. 01) . There were positive interactions between Helicobacter pylori infection and Pro12 Ala ( PA) , Pro12 Ala ( AA) , Pro198 Leu ( PL) , and Pro198 Leu ( LL) ( all γ > 1) . Conclusion The carriers of Pro12 Ala ( PA) , Pro12 Ala ( AA) , Pro198 Leu ( PL) , and Pro198 Leu ( LL) genotypes may have a high risk of NAFLD, and the interaction between these genotypes and Helicobacter pylori infection promotes the development and progression of NAFLD. Therefore, effective prevention measures including Helicobacter pylori eradication and gene expression regulation should be adopted to prevent NAFLD.