Role of TM6SF2 rs58542926 in the pathogenesis of nonalcoholic pediatric fatty liver disease: A multiethnic study.
Role of TM6SF2 rs58542926 in the pathogenesis of nonalcoholic pediatric fatty liver disease: A multiethnic study.
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DOI：
10.1002/hep.28283
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Santoro N
中科院分区：
文献类型：
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作者：
Goffredo M;Caprio S;Feldstein AE;D'Adamo E;Shaw MM;Pierpont B;Savoye M;Zhao H;Bale AE;Santoro N
评估跨膜6超家族成员2 （TM6SF2）基因rs58542926单核苷酸多态性（SNP）与肥胖青年脂肪肝疾病的关系。我们对957名肥胖儿童和青少年的多种族队列（42%的高加索人，28%的非洲裔美国人，30%的西班牙裔美国人）的TM6SF2 rs58542926 SNP进行了基因分型。所有患者均接受了口服葡萄糖耐量试验、肝脏检查和血脂检查。其中，454名儿童接受了MRI研究以评估肝脏脂肪含量（HFF%）， 11名儿童接受了肝活检以评估疾病严重程度。rs58542926 SNP的小等位基因与白种人和非裔美国人的高HFF%相关（均P<0.05），与西班牙裔美国人的高ALT水平相关（P<0.05），与白种人和西班牙裔美国人更有利的脂蛋白谱（低LDL、小密度LDL和非常小的LDL）相关（均P<0.05）。肝活检显示，携带该次要等位基因的受试者的纤维化患病率（P=0.04）和NAFLD活动评分（P=0.05）高于携带普通等位基因的受试者。此外，我们观察到TM6SF2 rss58542926、PNPLA3 rs738409和GCKR rs1260326 snp在决定肝内脂肪积累方面的联合作用（P<0.05）。TM6SF2基因中的rs58542926 SNP与儿童NAFLD相关，但可能具有预防心血管风险的作用。
To assess the association between the single-nucleotide polymorphism (SNP) rs58542926 in the transmembrane 6 superfamily member 2 (TM6SF2) gene and fatty liver disease in obese youth. We genotyped the TM6SF2 rs58542926 SNP in a multiethnic cohort of 957 obese children and adolescents (42% Caucasians, 28% African Americans, 30% Hispanics). All underwent an oral glucose tolerance test, a liver panel and a lipid profile. Of them, 454 children underwent a MRI study to assess hepatic fat content (HFF%), 11 children underwent liver biopsy to assess the degree of disease severity. The minor allele of the rs58542926 SNP was associated with high HFF% in Caucasians and African Americans (all P<0.05), with high ALT levels in Hispanics (P<0.05) and with a more favorable lipoprotein profile (lower LDL, small dense LDL and very small LDL) in Caucasians and Hispanics (all P<0.05). The liver biopsy showed a higher prevalence of fibrosis (P=0.04) and a higher NAFLD Activity Score (P=0.05) in subjects carrying the minor allele than in those homozygous for the common allele. Moreover, we observed a joint effect among the TM6SF2 rs58542926, the PNPLA3 rs738409 and the GCKR rs1260326 SNPs in determining intrahepatic fat accumulation (P<0.05). The rs58542926 SNP in the TM6SF2 gene is associated with pediatric NAFLD, but may confer protection against cardiovascular risk.