Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent
Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent
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DOI：
10.1038/ijo.2009.216
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发表时间：
2010-01-01
影响因子：
4.9
通讯作者：
Baroni, M. G.
中科院分区：
文献类型：
--
作者：
Romeo, S.;Sentinelli, F.;Baroni, M. G.
背景：PNPLA3 I148M变异(Rs738409)与肝脏脂肪变性密切相关。有趣的是，在平均体重指数(BMI)为30 kg m(-2)的队列中的初步发现也表明，PNPLA3变异与肝酶升高有关，但与胰岛素抵抗和血脂异常无关。目的：确定PNPLA3变异是否改变了病态肥胖受试者发生肝损伤和代谢后遗症的易感性。参与者和方法：这项研究是在678名意大利肥胖者(平均BMI 41 kg m(-2))中进行的，他们的I148M变异基因分型。所有参与者都提供了空腹血样，然后接受了口服葡萄糖耐量测试。主要观察指标：肝损伤指标(丙氨酸氨基转移酶、天冬氨酸氨基转移酶)、糖耐量和胰岛素抵抗。结果：148M等位基因携带者的ALT、AST等肝损伤指标明显高于对照组(P分别为2.2x10(-5)和0.001)。总体而言，50%的148M风险等位基因纯合子有病理水平的ALT(>；40Ul(-1))，而148I等位基因纯合子有25%的ALT水平(P=0.005)。结论：携带148M等位基因的肥胖南欧人肝损伤指数增加，与胰岛素抵抗的替代指标无关。《国际肥胖杂志》(2010年)34期，第190-194期；DOI：10.1038/ijo.2009.216；2009年10月20日在线出版
Context: The PNPLA3 I148M variant (rs738409) is robustly associated with hepatic steatosis. Intriguingly, initial findings in cohorts with a mean body mass index (BMI) of 30 kg m(-2) also suggested that it is associated with elevated liver enzymes but not with insulin resistance and dyslipidaemia.Objective: To determine whether the PNPLA3 variant alters the susceptibility of morbidly obese subjects to develop liver injury and metabolic sequelae.Participants and methods: The study was carried out in 678 obese Italians (mean BMI 41 kg m(-2)) who were genotyped for the I148M variant. All participants provided fasting blood samples and then underwent oral glucose tolerance tests. Main outcome measures: Indices of liver injury (alanine transaminase (ALT), aspartate transaminase (AST)), glucose tolerance and insulin resistance were measured.Results: Markers of hepatic injury such as ALT and AST were significantly higher in carriers of the 148M allele (P = 2.2 x 10(-5) and 0.001, respectively). In all, 50% of 148M risk allele homozygotes had pathological levels of ALT (> 40 Ul(-1)) compared with 25% of 148I allele homozygotes (P = 0.005). Glucose tolerance and insulin sensitivity were similar in all three genotypes.Conclusion: Obese Southern Europeans carrying the 148M allele have increased indices of liver damage uncoupled from proxy measures of insulin resistance. International Journal of Obesity (2010) 34, 190-194; doi:10.1038/ijo.2009.216; published online 20 October 2009