The 148M allele of the PNPLA3 gene is associated with indices of liver damage early in life
The 148M allele of the PNPLA3 gene is associated with indices of liver damage early in life
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DOI：
10.1016/j.jhep.2010.02.034
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发表时间：
2010-08-01
影响因子：
25.7
通讯作者：
Baroni, Marco G.
中科院分区：
文献类型：
--
作者：
Romeo, Stefano;Sentinelli, Federica;Baroni, Marco G.
背景与目的：儿童肥胖是一个日益严重的世界性问题。非酒精性脂肪性肝病（NAFLD）通常与儿童肥胖有关。最近，PNPLA 3基因I148 M（rs738409）变异被证明与肥胖成人的肝脂肪变性密切相关。在这项研究中，我们增加了进一步了解PNPLA 3的作用，探索这种关联是否开始在生活中的肥胖儿童或变得明显，只有在adult.Methods：四百七十五肥胖/超重的儿童和青少年的I148 M等位基因进行基因分型。收集所有参与者的临床和生化参数，包括肝损伤、葡萄糖耐量和胰岛素抵抗指数。超声成像的肝脏脂肪变性的程度进行评估，在一个子集的childh.Results：载体的两个148 M等位基因有一个52%的循环ALT水平增加相比，载体的两个148 I等位基因，与个人与一个148 M等位基因显示出9.5%的增加（p = 0.001）。两个和一个M等位基因携带者的AST浓度也显著较高（分别为17.4%和4%，p = 0.022）。两个148 M等位基因携带者中，ALT升高（定义为> 30 U/L）的比例为36%，而两个148 I等位基因携带者中，ALT升高的比例仅为10%（p <0.05）。
Background & aims: Childhood obesity is a growing problem worldwide. Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity in children. Recently, the PNPLA3 gene I148M (rs738409) variant was demonstrated to be strongly associated with hepatic steatosis in obese adults. In this study we add further insight into the role of PNPLA3 by exploring whether this association begins early in life in obese children or becomes manifest only in adulthood.Methods: Four hundred and seventy-five obese/overweight children and adolescents were genotyped for the I148M allele. Clinical and biochemical parameters were collected for all participants, including indices of hepatic injury, glucose tolerance and insulin resistance. Ultrasound imaging of the liver was obtained to assess the degree of steatosis in a subset of children.Results: Carriers of two 148M alleles had a 52% increase in circulating ALT levels compared to carriers of two 148I alleles, with individuals with one 148M allele showing a 9.5% increase (p = 0.001). AST concentration was also significantly higher in carriers of two and one M alleles (17.4% and 4%, respectively, p = 0.022). A total of 36% of carries of two 148M alleles showed elevated ALT, defined as >30U/L, compared to only 10% of carriers of two 148I alleles (p