The Membrane-bound O-Acyltransferase7 rs641738 Variant in Pediatric Nonalcoholic Fatty Liver Disease
The Membrane-bound O-Acyltransferase7 rs641738 Variant in Pediatric Nonalcoholic Fatty Liver Disease
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DOI：
10.1097/mpg.0000000000001979
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发表时间：
2018-07-01
影响因子：
2.9
通讯作者：
del Giudice, Emanuele Miraglia
中科院分区：
文献类型：
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作者：
Di Sessa, Anna;Umano, Giuseppina Rosaria;del Giudice, Emanuele Miraglia
背景：膜结合酰基转移酶结构域蛋白7 （MBOAT7）基因的rs641738多态性与非酒精性脂肪性肝病（NAFLD）的风险增加有关。目的：探讨MBOAT7 rs641738多态性与肝脂肪变性和肝损伤生化标志物的关系，并评价该变异与I148M类patin -like phospholipase domain containing 3 （PNPLA3）和rs58542926跨膜6超家族成员2 （TM6SF2）多态性的潜在加性作用。方法：采用MBOAT7、PNPLA3、TM6SF2多态性基因分型方法，对1000名肥胖儿童进行人体测量、超声和生化评价。计算间接测量肝纤维化（小儿NAFLD纤维化指数[PNFI]）和这些多态性的遗传风险评分。结果：mboat7t等位基因携带者的谷丙转氨酶（ALT） （P = 0.004）和PNFI值（P = 0.04）均高于非携带者。与非携带者相比，MBOAT7 T等位基因多态性携带者与肝脂肪变性患者也证实了这些发现。遗传风险评分越高，ALT越高（P = 0.011）， ALT升高的比值比（OR）为3.4 （95% CI 1.3-5.5, P = 0.003）。遗传风险评分3分组与低遗传风险评分组相比，出现脂肪变性的OR为2.6 （95% CI 1.43 ~ 4.83, P = 0.0018）。结论：我们首次在儿童肥胖中证实了MBOAT7 rs641738变异对血清ALT的作用，以及MBOAT7、PNPLA3和TM6SF2变异对NAFLD风险的综合影响。我们还首次提供了MBOAT7多态性与肝纤维化间接标志物的儿科关联。
Background: The rs641738 polymorphism in the membrane-bound Oacyltransferase domain containing protein 7 (MBOAT7) gene has been associated with increased risk of nonalcoholic fatty liver disease (NAFLD).Objectives: To investigate the association between the MBOAT7 rs641738 polymorphism and both hepatic steatosis and biochemical markers of liver damage and to evaluate the potential additive effect of this variant and the I148M patatin-like phospholipase domain-containing 3 (PNPLA3) and the rs58542926 transmembrane 6 superfamily member 2 (TM6SF2) polymorphisms.Methods: One thousand and 2 obese children were genotyped for MBOAT7, PNPLA3, and TM6SF2 polymorphisms and underwent anthropometncal, ultrasonographic, and biochemical evaluation. Indirect measurement of liver fibrosis (Pediatric NAFLD Fibrosis Index [PNFI]) and a genetic risk score from these polymorphisms were calculated.Results: Carriers of the MBOAT7 T allele showed both higher alanine transaminase (ALT) (P = 0.004) and PNFI values (P = 0.04) than noncarriers. These findings were confirmed also for the carriers of the MBOAT7 T allele polymorphism with hepatic steatosis compared with noncarriers. A higher genetic risk score was associated with higher ALT (P = 0.011) and with an odds ratio (OR) to show elevated ALT of 3.4 (95% CI 1.3-5.5, P = 0.003). Patients belonging to genetic risk score 3 group had an OR to present steatosis of 2.6 (95% CI 1.43-4.83, P = 0.0018) compared with those belonging to lower genetic risk score group.Conclusions: We first demonstrated in childhood obesity the role of the MBOAT7 rs641738 variant on serum ALT and the combined effect of the MBOAT7, PNPLA3, and TM6SF2 variants on NAFLD risk. We also provided the first pediatric association of the MBOAT7 polymorphism with indirect markers of liver fibrosis.