临床儿科杂志 ›› 2017, Vol. 35 ›› Issue (4): 241-.doi: 10.3969/j.issn.1000-3606.2017.04.001

• 营养消化系统专栏 •    下一篇

脂质代谢相关基因变异与肥胖儿童非酒精性脂肪肝易感性分析

代东伶1, 2, 周少明1, 柳国胜2, 文飞球1, 周建利1   

  1. 1. 深圳市儿童医院( 广东深圳 518036 ) ;2 . 暨南大学第一医院(广东广州 510630)
  • 收稿日期:2017-04-15 出版日期:2017-04-15 发布日期:2017-04-15
  • 通讯作者: 周少明  E-mail:zhousm15 d@aliyun.com
  • 基金资助:
    深圳市科创委创新基金项目(No.JCYJ20150403100317080)

Variation in genes related to lipid metabolism and the susceptibility of nonalcoholic fatty liver disease in obese children 

 DAI Dongling 1,2 , ZHOU Shaoming1, LIU Guosheng2, WEN Feiqiu1, ZHOU Jianli1   

  1. 1. Shenzhen Children's Hospital, Shenzhen 518036, Guangdong, China;2. First Affiliated Hospital of Jinan University, Guangzhou 510630, Guangdong, China
  • Received:2017-04-15 Online:2017-04-15 Published:2017-04-15

摘要: 目的 探讨儿童脂质代谢相关基因变异与非酒精性脂肪肝(NAFLD)易感性。方法 纳入6~18岁的肥胖伴脂 肪肝儿童,进行超声检查、常规体检及生化检测,并提取外周血 DNA,对36个脂质代谢相关目标基因进行二代测序,分析 这些基因变异与脂肪肝的相关性。结果 符合纳入标准的368例肥胖儿童中检出NAFLD 183例,占比为49.7%。在肥胖 儿童中随机选取NAFLD及non-NAFLD各100例,NAFLD儿童的体质量、腰围、丙氨酸氨基转移酶(ALT)、三酰甘油(TG)、 胆固醇、低密度脂蛋白(LDL)和载脂蛋白B(ApoB)均高于non-NAFLD儿童,两组比较差异有统计学意义(P均<0.05); 而两组间天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、载脂蛋白A1(ApoA1)、空腹血糖、胰岛素、高密度脂蛋白(HDL)、 游离脂肪酸(FFA)以及稳态模型胰岛素抵抗指数(HOMA-IR)的差异均无统计学意义(P均>0.05);两组的胆红素水平均 在正常范围。Logistic回归分析发现,编码微粒体三酰甘油转运蛋白(MTTP或MTP)的基因MTTP rs2306986(OR=2.70, 95%CI:1.38~5.27)、MTTP rs3792683(OR=7.34,95%CI:2.04~26.50)及编码含patatin样磷脂酶域3的基因PNPLA3 rs738409位点变异(OR=2.11,95%CI:1.31~4.48)是影响NAFLD发生的独立危险因素。结论 MTTP rs2306986、MTTP rs3792683、PNPLA3 rs738409基因变异可能增加儿童NAFLD易感性。

Abstract:  Objective To explore the association between variation in genes related to lipid metabolism and the susceptibility of nonalcoholic fatty liver disease (NAFLD). Methods Obese children with fatty liver aged 6~18 years old were included. All of them got ultrasonic testing, routine examination and biochemical detection. In addition, the DNA of peripheral blood was extracted and the 36 target genes related to lipid metabolism were detected by next generation sequencing.  Results In 368  obese children who met the inclusion criteria, 183 children (49.7%) were detected to have NAFL . 100 children with NAFLD and 100 children without NAFLD were randomly selected from obese children. The levels of body mass, waistline, alanine aminotransferase (ALT),  triacylglycerol (TG), cholesterol, low density lipoprotein (LDL) and apolipoprotein B (ApoB) in NAFLD children were all higher than those in non-NAFLD children, and there were significant differences (P all<0.05). However, the levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), apolipoprotein A1 (ApoA1), fasting blood glucose, insulin, high density lipoprotein (HDL), free fatty acid (FFA) and insulin resistance index (HOMA-IR) were not significantly different between the two groups (P all>0.05). The levels of bilirubine in the two groups were within normal range. Logistic regression analysis showed that the genes of MTTP rs2306986 (OR=2.70, 95%CI: 1.38~5.27) and MTTP rs3792683 (OR=7.34, 95%CI: 2.04~26.50) that encode microsomal triglyceride transfer protein (MTTP or MTP), and the mutation of rs738409 (OR=2.11, 95%CI:1.31~4.48) in gene PNPLA3 that encode patatin-like phospholipase domain-containing protein 3 are the independent risk factors for the occurrence of the disease. Conclusion Genovariation of MTTP rs2306986, MTTP rs3792683, and PNPLA3 rs738409 may increase susceptibility to NAFLD in children.