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χ^2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,并分析Pro12Ala、Pro198Leu多态性与H. pylori感染的交互作用。结果 Pro12Ala(PA)、Pro12Ala(AA)、Pro198Leu(PL)和Pro198Leu(LL)基因型者患NAFLD的风险均显著增加(OR分别为5. 7324、5. 973 2、6. 360 5、6. 165 7,P值均<0. 01)。基因突变的协同分析发现在Pro12Ala(PA)和Pro198Leu(PL)之间、Pro12Ala(PA)和Pro198Le(LL)之间、Pro12Ala(AA)和Pro198Leu(PL)及Pro12Ala(AA)和Pro198Leu(LL)之间均存在正向交互作用(γ值均> 1)。100≤DPM <500和DPM≥500的H. pylori感染者患NAFLD的风险性均明显增高(ORNAFL=2. 064 1,ORNASH=4. 448 5,ORNAFHC=10.969 5;ORNAFL=3. 130 5,ORNASH=8. 024 6,ORNAFHC=21. 461 4),而DPM≥500的H. pylori感染者患NAFLD的风险性则又明显高于100≤DPM <500的H. pylori感染者(P <0. 01)。H. pylori感染与Pro12Ala(PA)、Pro12Ala(AA)、Pro198Leu(PL)和Pro198Leu(LL)基因型均有正向交互作用(γ值均>1)。结论携带Pro12Ala(PA)、Pro12Ala(AA)、Pro198Leu(PL)和Pro198Leu(LL)基因型的个体属NAFLD高危险人群,这些基因型和H. pylori感染的交互作用促进了NAFLD的发生、发展,应当采取根除H. pylori或调控基因表达的措施以达到有效预防NAFLD的目的。
Objective To investigate the 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 (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 July 2015 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 Pro12Ala and Pro198Leu. The 14 C-urea breath test was used to measure disintegration per minute (DPM) of Helicobacter pylori binding to 14 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 Pro12Ala polymorphism, Pro198Leu 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 Pro12Ala and GPx-1 gene Pro198Leu was analyzed. Results The patients with the genotypes of Pro12Ala (PA), Pro12Ala (AA), Pro198Leu (PL), and Pro198Leu (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 Pro12Ala (PA) and Pro198Leu (PL), between Pro12Ala (PA) and Pro198Leu (LL), between Pro12Ala (AA) and Pro198Leu (PL), and between Pro12Ala (AA) and Pro198Leu (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: OR NAFL =2.064 1, OR NASH =4.448 5, OR NAFHC =10.969 5;DPM≥500: OR NAFL = 3.130 5, OR NASH =8.024 6, OR NAFHC =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 Pro12Ala (PA), Pro12Ala (AA), Pro198Leu (PL), and Pro198Leu (LL)(all γ>1). Conclusion The carriers of Pro12Ala (PA), Pro12Ala (AA), Pro198Leu (PL), and Pro198Leu (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.
作者
张超贤
郭李柯
张利利
李光艳
常廷民
ZHANG Chaoxian;GUO Like;ZHANG Lili(Department of Gastroenterology,The First Affiliated Hospital of Xinxiang Medical University,Weihui,Henan 453100,China)
出处
《临床肝胆病杂志》
CAS
北大核心
2019年第7期1551-1559,共9页
Journal of Clinical Hepatology
基金
河南省教育厅科研基金项目(2011A320015)
