METHODS: A total of 1047 children and 2057 adults were included. DNA was genotyped for rs738409 in duplicate. Primary outcome of interest was advanced fibrosis (fibrosis stage ≥3). Regression analyses were performed after controlling for relevant covariates. An additive model was used to assess the effect of PNPLA3 G-allele (CC vs CG vs GG).
RESULTS: PNPLA3 G-allele was significantly associated with advanced fibrosis in children (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.16-2.09) and adults (OR, 1.55; 95% CI, 1.16-1.54). Across the cohort, older age significantly increased the risk for advanced fibrosis for PNPLA3 CC (OR, 1.019; 95% CI, 1.013-1.026), CG (OR, 1.024; 95% CI, 1.018-1.030), and GG (OR, 1.03; 95% CI, 1.023-1.037) genotypes. BMI significantly increased the relationship between PNPLA3 genotypes and advanced fibrosis in children and adults. A BMI of 30 kg/m2 was the cutoff beyond which PNPLA3 G-allele had exponential effect on the risk for advanced fibrosis in children and adults. T2DM significantly worsened the relationship between PNPLA3 G-allele and advanced fibrosis in children and adults (interaction P < .01 for both).
CONCLUSIONS: Age, BMI, and T2DM modify the risk of advanced fibrosis associated with PNPLA3 G-allele. Preventing or reversing T2DM and obesity in persons carrying PNPLA3 G-allele may lower the risk for advanced fibrosis in NAFLD.
方法:纳入1,047名儿童和2,057名成人。对rs738409的DNA进行基因分型,一式两份。感兴趣的主要结果是晚期纤维化(纤维化分期≥3)。在控制相关协变量后进行回归分析。使用加性模型来评估PNPLA3G等位基因(CCvsCGvsGG)的作用。
结果:PNPLA3G等位基因与儿童(OR:1.55,95%CI:1.16-2.09)和成人(OR:1.55,05%CI:1.16-1.54)的晚期纤维化显著相关。在整个队列中,老年显著增加了PNPLA3CC晚期纤维化的风险(OR:1.019,95%CI:1.013-1.026),CG(OR:1.024,95%CI:1.018-1.030),和GG(OR:1.03,95%CI:1.023-1.037)基因型。BMI显著增加PNPLA3基因型与儿童和成人晚期纤维化之间的关系。30kg/m2的BMI是临界值,超过该临界值,PNPLA3G等位基因对儿童和成人的晚期纤维化风险具有指数效应。在儿童和成人中,T2DM均显著恶化了PNPLA3G等位基因与晚期纤维化之间的关系(两者的交互作用P<0.01)。
结论:年龄,BMI,和T2DM改变与PNPLA3G等位基因相关的晚期纤维化风险。在携带PNPLA3G等位基因的人中预防或逆转T2DM和肥胖可能降低NAFLD中晚期纤维化的风险。