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幽门螺杆菌感染与PPARγ2基因Pro12Ala、GPx-1基因Pro198Leu多态性的交互作用和非酒精性脂肪性肝病的关系
DOI: 10.3969/j.issn.1001-5256.2019.07.026
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
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摘要:
目的探讨幽门螺杆菌（H. pylori）感染与过氧化物酶体增殖物激活受体γ2（PPARγ2）基因Pro12Ala、谷胱甘肽过氧化物酶-1（GPx-1）基因Pro198Leu多态性的交互作用和非酒精性脂肪性肝病（NAFLD）及其严重程度的关系。方法选择2011年3月-2015年7月新乡医学院第一附属医院门诊和病房收治的非酒精性单纯性脂肪肝（NAFL）、非酒精性脂肪性肝炎（NASH）和非酒精性脂肪性肝硬化（NAFHC）患者各750例,以750例健康体检者作为对照组,以上述各组患者的外周血白细胞为样本,利用PCRRFLP技术检测了Pro12Ala和Pro198Leu多态性。采用14C-尿素呼气试验法检测受检者H. pylori与14C结合的每分钟衰变数（DPM）以判断H. pylori感染情况;对每位研究对象进行面对面的问卷调查。计量资料2组间比较采用t检验;计数资料组间比较采用χ2检验。采用多因素logistic回归模型对资料进行分析,估算PPARγ2基因Pro12Ala和GPx-1基因Pro198Leu多态性和H. pylori感染与NAFLD发病风险的调整比值比（OR）及95%可信区间...
Abstract: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.
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