慢性HBV感染者外周血PNPLA3/PRKAA1基因多态性与肝硬化发生关系研究

Polymorphisms of PNPLA3 and PRKAA1 genes and their correlation to liver cirrhosis in patients with hepatitis B viral infection

目的探讨Patatin样磷脂酶域蛋白3(PNPLA3)和腺苷活化蛋白激酶α1亚基(PRKAA1)基因多态性与感染HBV后肝硬化发生的关系。方法2016年1月~2021年7月我院诊治的乙型肝炎肝硬化患者101例和同期慢性无症状HBV携带者90例,采用聚合酶链反应-限制性片段长度多态性检测血浆PNPLA3基因rs738409、rs139047、rs2294919和PRKAA1基因rs3792822、rs10036575、rs154268位点多态性,应用Logistic回归分析疾病风险关联。结果肝硬化组PNPLA3基因rs139047位点AA、GA、GA基因型比率分别为18.8%、51.5%和29.7%,与HBV携带者的16.7%、51.1%和32.2%比,无显著性差异(P>0.05),rs2294919位点CC、TC、TT基因型比率分别为41.6%、45.5%和12.9%,与HBV携带者的38.9%、50.0%和11.1%比,无显著性差异(P>0.05);PRKAA1基因rs3792822位点GG、GA、AA基因型比率分别为54.5%、38.6%和6.9%,与HBV携带者的55.6%、37.8%和6.7%比,无显著性差异(P>0.05),rs154268位点CC、CT、TT基因型比率分别为5.0%、35.6%和59.4%,与HBV携带者的4.4%、34.4%和61.1%比,无显著性差异(P>0.05);肝硬化组PNPLA3基因rs738409位点GG基因型和等位基因G比率分别为19.8%和44.6%,显著高于HBV携带者的8.9%和29.4%(P<0.05);肝硬化组PRKAA1基因rs10036575位点CC基因型和等位基因C比率分别为38.6%和63.9%,显著高于HBV携带者的23.3%和45.5%(P<0.05);经非条件Logistic回归模型分析显示PNPLA3基因rs738409位点GG基因型【OR为1.605(95%CI:1.150~2.239)】和PRKAA1基因rs10036575位点CC基因型【OR值为1.507((95%CI:1.097~2.070)】是影响感染HBV后肝硬化发生的危险基因型。结论感染HBV后发生肝硬化可能与某些特殊基因有关,研究PNPLA3基因和PRKAA1基因可能有助于阐明其中的分子机制。

Objective The aim of this study was to explore the polymorphisms of patatin-like phospholipase domain-containing protein 3(PNPLA3)and protein kinase AMP-activated catalytic subunitα1(PRKAA1)genes and their correlation to liver cirrhosis in patients with hepatitis B viral infection.Methods A total of 101 patients with hepatitis B-induced liver cirrhosis and 90 asymptomatic HBV carriers were enrolled in our hospital between January 2016 and July 2021.The polymorphisms of PNPLA3 gene at rs738409,rs139047 and rs2294919 loci,and PRKAA1 gene at rs3792822,rs10036575 and rs154268 loci were detected by polymerase chain reaction-restriction fragment length polymorphism.The correlation of suspected genes and tendency of cirrhosis was explored by Logistic regression analysis.Results The percentages of AA,GA and GA genotypes of gene PNPLA3 at rs139047 locus in patients with cirrhosis were 18.8%,51.5%and 29.7%,not statistically significantly different compared with 16.7%,51.1%and 32.2%in HBV carriers(P>0.05);the percentages of CC,TC and TT genotypes of gene PNPLA3 at rs2294919 locus in patients with cirrhosis were 41.6%,45.5%and 12.9%,not significantly different compared with 38.9%,50.0%and 11.1%in HBV carriers(P>0.05);the percentages of GG,GA and AA genotypes of gene PRKAA1 at rs3792822 locus in patients with cirrhosis were 54.5%,38.6%and 6.9%,not statistically significant compared with 55.6%,37.8%and 6.7%in HBV carriers(P>0.05);the percentages of CC,CT and TT genotypes of gene PRKAA1 at rs154268 locus in patients with cirrhosis were 5.0%,35.6%and 59.4%,not statistically significant compared with 4.4%,34.4%and 61.1%in HBV carriers(P>0.05);the percentage of GG genotype and allele G of PNPLA3 gene at rs738409 locus in patients with cirrhosis were 19.8%and 44.6%,significantly higher than 8.9%and 29.4%,respectively,in HBV carriers(P<0.05),and the percentage of CC genotype and allele C of PRKAA1 gene at rs10036575 locus were 38.6%and 63.9%,significantly higher than 23.3%and 45.5%,respectively,in HBV carriers(P<0.05);the unconditional Logistic regression model analysis showed that the GG genotype of PNPLA3 gene at rs738409 locus[OR=1.605(95%CI:1.150-2.239)]and CC genotype of PRKAA1 gene at rs10036575 locus[OR=1.507((95%CI:1.097-2.070)]were the risk genotype for cirrhosis occurrence.Conclusion The individuals with HBV infections and susceptible genes might have a high tendency of liver cirrhosis,and the polymorphism of PNPLA3 and PRKAA1 genes might have a correlation to the involved pathogenesis.