PNPLA3基因多态性与非酒精性脂肪性肝病关系的初步探讨

目的 分析PNPLA3基因多态性与非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的关系,探讨PNPLA3 rs738409G突变基因携带者NAFLD发生的危险因素,为预防NAFLD的发生提供理论依据。方法 收集航天中心医院2012年～2013年体检者共617例,包括324例健康者和293例NAFLD患者。采用实时荧光定量PCR法检测所有研究对象的rs738409分型,并采用Oneway ANOVA比较不同基因型组之间年龄,性别,BMI,TG,CHOL,hs-CRP,ALT,AST,FPG,HbA1c,CEA,AFP和CA19-9差异有无统计学意义。采用单因素方差分析比较健康组和NAFLD组之间部分生化检测指标和肿瘤标志物的表达水平差异有无统计学意义。Logistic回归分析用于评估rs738409G携带者NAFLD发生的危险因素。结果 ALT(U/L)在CC,CG和GG基因型中的血清水平分别是17.8(12.9,25.3),20.00(14.40,27.65)和20.2(14.85,38.8),表达水平逐渐增高,差异均具有统计学意义(P值均<0.05)。AST(U/L)在CC,CG和GG基因型中的血清水平分别是20.3(17.6,24.5),20.70(17.95,25.20)和22.3(18.60,29.65),仅在CC组和GG组(P=0.000)、CG和GG组(P=0.004)之间的差异具有统计学意义(P值均<0.05)。年龄,性别,BMI,TG,CHOL,hs-CRP,FPG,HbA1c,CEA,AFP和CA19-9在不同基因型的表达差异无统计学意义(P值均>0.05)。BMI(Kg/m²),ALT(U/L),AST(U/L),TG(mmol/L),hs-CRP(mg/ml),FPG(mmol/L)和HbA1c(%)在NAFLD患者组与健康对照组中的表达水平分别是[22.97±2.58 vs 26.74±2.35],[15.65(11.97,21.3)vs 24(17.55,35.4)],[19.8(17.3,23.5)vs 22(18.9,,27.35)],[0.99(0.75,1.40)vs 1.77(1.23,2.54)],[0.89(0.64,1.41)vs 1.43(0.96,2.51)],[4.88(4.61,5.21)vs 5.14(4.82,5.62)]和[5.50(5.3,5.7)vs 5.70(5.45,6.00)],差异均具有统计学意义(P值均<0.05)。Logistic回归分析结论显示,BMI,TG,ALT和HbA1c是rs738409G突变基因携带者NAFLD的危险因素,回归系数分别是0.707,2.968,2.765和21.301。结论 对于rs738409G突变基因健康携带者应该定期监测BMI,TG,ALT和HbA1c,预防NAFLD的发生。

Preliminary Discussion of the Relationshipbetween PNPLA3 Polymorphism and NAFLD

Objective To analyze the relationship between PNPLA3 polymorphism and NAFLD,detect the risk factors of NAFLD for healthy subjects with G allele at rs738409,and provide the theory basis for prevention of NAFLD.Methods 617 health examination subjects from 2012～2013 in Aerospace Center Hospital were enrolled in this study and divided into 2groups,324 healthy ones and 293 NAFLD patients.Real-time fluorescence quantitative PCR(RT-PCR)was used to detect genotype,while age,BMI,TG,CHOL,hs-CRP,ALT,AST,FPG,HbA1c,CEA,AFP and CA19-9 were analyzed among different genotype groups.One way ANOVA was applied to analyze BMI,TG,CHOL,hs-CRP,ALT,AST,FPG,HbA1c,CEA,AFP and CA19-9 between healthy subjects and NAFLD patients.Logistic regression was used to find out the NAFLD risk factors in healthyperson with G allele at rs738409.Results Serum ALT(U/L)levels in CC/CG/GG genotype groups were 17.8(12.9, 25.3),20.00(14.40,27.65)and 20.2(14.85,38.8),respectively,P<0.05.AST(U/L)levels in CC/CG/GG genotype groups were 20.3(17.6,24.5),20.70(17.95,25.20)and 22.3(18.60,29.65),but only difference in CC/GG and CG/GG was significant,andP value were 0.000 and 0.004 respectively.Differences of age,BMI,TG,CHOL,hs-CRP,FPG,HbA1c,CEA,AFP and CA19-9 among CC/CG/GG genotype groups were not significant,and all P values>0.05.BMI(Kg/m²),ALT(U/L),AST(U/L),TG(mmol/L),hs-CRP(mg/ml),FPG(mmol/L)and HbA1c(%)levels between healthy subjects and NAFLD patients were [22.97±2.58 vs 26.74±2.35],[15.65(11.97,21.3)vs 24(17.55,35.4)],[19.8(17.3,23.5)vs 22(18.9,27.35)],[0.99(0.75,1.40)vs 1.77(1.23,2.54)],[0.89(0.64,1.41)vs 1.43(0.96,2.51)],[4.88(4.61,5.21)vs 5.14(4.82,5.62)],[5.50(5.3,5.7)vs 5.70(5.45,6.00)], respectively,P<0.05,and the difference was statistically significant.BMI,ALT,TG and HbA1c were risk factorsof NAFLD for healthy person with G allele at rs738409 by logistic regression,and the regression coefficients were 0.707,2.968,2.765 and 21.301.Conclusion It is necessary for healthy person with G allele at rs738409 to monitor BMI,ALT,TG and HbA1c,which will reduce the incidence of NAFLD in the future.