儿童非酒精性脂肪性肝病相关的脂质代谢基因变异及生物学信息分析  

Genetic variation and biological information analysis of lipid metabolism associated with non-alcoholic fatty liver disease in children

作　　者：杨琴[1] 曾祥士[1] 代东伶[1] Yang Qin;Zeng Xiangshi;Dai Dongling(Department of Digestive,Shenzhen Children′s Hospital,Shenzhen 518038,Guangdong Province,China)

机构地区：[1]深圳市儿童医院消化科,广东深圳518038

出　　处：《中华实用儿科临床杂志》2019年第19期1458-1461,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：广东省医学科研基金(A2018550);深圳市科技创新委员会创新基金(JCYJ20150403100317080,JCYJ20180228175150018)。

摘　　要：目的研究儿童非酒精性脂肪性肝病(NAFLD)中与脂质代谢相关的基因变异及其生物学信息。方法收集2017年9月至2018年9月因肥胖在深圳市儿童医院消化科就诊且符合入选标准的100例儿童,其中男66例,女34例;年龄8~18岁。对纳入标准的100例肥胖儿童进行肝脏脂肪变性超声评分,分为NAFLD患儿(NAFLD组,39例)和肥胖健康儿童(对照组,61例)。采集受试儿童的血液样本进行外显子测序,研究参与脂质代谢的相关基因变异,并通过PPI分析、Go项富集分析进一步评价其生物学信息,采用软件对变异位点进行致病性预测分析。结果NAFLD组和对照组的性别和年龄比较差异均无统计学意义(均P>0.05)。2组体质量指数(BMI)和腰围比较,差异均有统计学意义(均P<0.000 1)。PPI分析提示微粒体甘油三酸酯转运蛋白、载脂蛋白B、肝脂肪酶存在直接相互作用。Go分析提示富集度最高为三酰甘油、酰基甘油、中性脂质、甘油醚和有机醚代谢途径(P<0.001)。NAFLD组中MTTP rs2306986(chr4:100504575:G>C)和MTTP rs3792683(chr4:100510903:A>G)位点变异检出率均明显高于对照组(均P=0.002),且rs2306986位点是可能致病的突变。结论本研究结果提示脂质代谢在NAFLD中起关键作用,MTTP中的rs2306986位点变异(chr4:100504575:G>C)与儿童患NAFLD风险增加相关。Objective To fully investigate the roles of gene variations associated with lipid metabolism in pediatric non-alcoholic fatty liver disease(NAFLD).Methods One hundred obese children who were admitted to the gastroenterology department of Shenzhen Children′s Hospital from September 2017 to September 2018 meeting the inclusion criteria were collected.There were 66 males and 34 females aged 8-18 years.Exon sequencing was performed on blood samples from 100 subjects including 39 children with NAFLD(NAFLD group)and 61 healthy obese children(control group).The mutations of genes in lipid metabolism were investigated,and the functions of the variants were further evaluated through PPI analysis and Go term enrichment analysis and software tools which could predicts possible impact on the structure and function of proteins.Results There were no significant differences between NAFLD and control group in gender and age(all P>0.05).Body mass index(BMI)and waist in the control group were significantly lower than those of NAFLD group(all P<0.000 1).PPI showed that protein microsomal triglyceride transfer protein microsomal triglyceride transfer protein(MTTP),apolipoprotein B(APOB)and Hepatic lipase C(LIPC)were directly interacted.Go analysis showed that the most enriched pathway were triacylglycerol,acylglycerol,neutral lipids,glycerol ether and organo ether(P<0.001).Two variants(chr4:100504575:G>C,chr4:100510903:A>G)located in MTTP were significantly differently distributed between 2 groups(all P=0.002),and a potential pathogenic mutation could exist in rs2306986 site.Conclusions The findings of this study indicate that lipid metabolism plays an important role in NAFLD and rs2306986 in MTTP was associated with higher susceptibility to NAFLD.

关 键 词：儿童 非酒精性脂肪性肝病 基因变异 脂质代谢 生物学信息 

分 类 号：R57[医药卫生—消化系统]