PPARGC1A rs8192678 G>A polymorphism affects the severity of hepatic histological features and nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease

BACKGROUND The association between PPARGC1A rs8192678 and nonalcoholic fatty liver disease(NAFLD)requires further confirmation.In addition,it is still unknown whether PPARGC1A rs8192678 is associated with hepatic histological features in NAFLD in the Chinese population.AIM To investigate the interaction between PPARGC1A rs8192678 and nonalcoholic steatohepatitis(NASH),and whether this polymorphism is associated with hepatic histological features.METHODS Fifty-nine patients with liver biopsy-proven NAFLD and 93 healthy controls were recruited to a cohort representing the Chinese Han population.The SAF(steatosis,activity,and fibrosis)scoring system was used for hepatic histopathological evaluation.The polymorphisms of PPARGC1A rs8192678 and patatin-like phospholipase domain-containing protein 3(PNPLA3)rs738409 were genotyped.The intrahepatic mRNA expression of PPARGC1A was evaluated by real-time polymerase chain reaction.RESULTS Thirty-seven patients with NAFLD had NASH,of which 12 were nonobese.The PPARGC1A rs8192678 risk A allele(carrying GA and AA genotypes)had the lowest P value in the dominant model;the odds ratio(OR)for NAFLD was 2.321[95%confidence interval(CI):1.121-4.806].After adjusting for age,sex,and the PNPLA3 rs738409 risk G allele,the PPARGC1A rs8192678 A allele was a risk factor for NAFLD(OR 2.202,95%CI:1.030-4.705,P=0.042).The genetic analysis showed that patients with NAFLD,moderate-to-severe steatosis(S2-3),and Activity 2-4(A≥2)were more likely to carry A in PPARGC1A rs8192678(OR 5.000,95%CI:1.343-18.620,P=0.012;and OR 4.071,95%CI:1.076-15.402,P=0.031).The multivariate logistic regression analysis showed that PPARGC1A rs8192678 risk A allele was also independently associated with S2-3,A≥2,and NASH(OR 6.190,95%CI:1.508-25.410,P=0.011;OR 4.506,95%CI 1.070-18.978,P=0.040;and OR 6.337,95%CI:1.135-35.392,P=0.035,respectively)after adjusting for age,sex,body mass index,and PNPLA3 rs738409 risk G allele.The results also showed that this polymorphism was associated with nonobese NASH(OR 22.000,95%CI:1.540-314.292,P=0.021).The intrahepatic expression of PPARGC1A mRNA was significantly lower in the group of patients who carried the risk A allele(P=0.014).CONCLUSION The PPARGC1A rs8192678 risk A allele is associated with NAFLD,and with S2-3,A≥2 and NASH in NAFLD patients,independent of PNPLA3 rs738409,and may be associated with nonobese NASH.

PGC-1α基因及其单核苷酸多态性与糖尿病肾病的相关性

目的:探讨糖尿病肾病(DKD)易感性与过氧化物酶体增殖物激活受体γ辅助激活因子(PGC)-1α基因SNP位点rs8192678的相关性。方法:招募200例糖尿病(DM)患者,无肾脏病损伤,200例DKD患者。利用DNA提取试剂盒提取患者外周血DNA,应用TaqMan-MGB探针法对SNP rs8192678进行基因分型,分析PGC-1α基因rs8192678(G>A)等位基因分布,并评估其与DKD易感性的相关性。利用实时定量PCR检测DM患者和DKD患者血液PGC-1αmRNA表达与rs8192678基因多态性之间的关系。观察不同中医证型DKD患者rs8192678等位基因及基因型频率分布。结果:PGC-1α基因rs8192678基因型GG在DM中比例较DKD更少见(47.5%比72.5%,P<0.001)。在三个遗传模型(加性、显性和隐性)中,在年龄和性别校正后,GG基因型与较高的DKD风险相关(P=0.000)。在DM组和DKD组全血中,AA基因型患者PGC-1αmRNA水平显著高于GG基因型(P<0.01)。PGC1-α基因rs8192678位点的等位基因中,G等位基因频率在所有DKD证型中均较A等位基因频率高。DKD患者中医证候由阴虚燥热证逐渐转向阴阳两虚证过程中,患者GG表达占比逐渐增多。结论:rs8192678的风险相关G等位基因与DKD相关,G等位基因增加了DKD风险,且DKD患者中医证候分型与PGC1-α基因rs8192678多态性位点有内在关系。

PPARGC1A基因多态性与中国汉族人群2型糖尿病患者肾脏疾病风险的研究

目的:探讨糖尿病(diabetes mellitus,DM)患者中PPARGC1A rs8192678(G>A)基因多态性与糖尿病肾病(Diabetic kidney disease,DKD)风险的相关性。方法:利用TaqMan SNP基因分型分析DM与DKD患者rs8192678基因多态性,进行卡方检验和多变量逻辑回归分析,评估rs8192678与DKD易感性之间的关联。结果:次要等位基因(A)与DKD低风险之间存在显著相关性(P<0.02)。在显性模型中,与GG基因型相比,GA+AA基因型的DKD风险显着降低(P=0.007);在加性模型中,与GG基因型相比,GA和AA基因型的DKD风险显着降低(P=0.027)。在亚组分析中,TC正常组显性模型GG较GA+AA基因型的DKD风险显着降低(P=0.018);在TG正常组显性模型中,GG较GA+AA基因型的DKD风险显着降低(P=0.001);在加性模型中,GG较GA和AA基因型的DKD风险显着降低(P=0.001)。结论:中国汉族人群糖尿病患者中PPARGC1A rs8192678等位基因A与DKD的低风险显著相关。