PDF(Pubmed)
Abstract：
OBJECTIVE: PNPLA3 G-allele is an important determinant of disease severity in nonalcoholic fatty liver disease (NAFLD). Here, we investigated the effect of age, body mass index (BMI), and type 2 diabetes mellitus (T2DM) on the relationship between PNPLA3 G-allele and advanced fibrosis in adults and children with histologically characterized NAFLD.
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.
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.
摘要：
目的：PNPLA3G等位基因是NAFLD疾病严重程度的重要决定因素。这里,我们调查了年龄的影响，BMI,2型糖尿病（T2DM）对PNPLA3G等位基因与组织学特征NAFLD的成人和儿童晚期纤维化之间的关系。
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。
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。
