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

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

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 rs 3792683(OR=7.34,95%CI:2.04~26.50)及编码含patatin样磷脂酶域3的基因PNPLA3rs 738409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 rs 2306986、MTTP rs 3792683、PNPLA3 rs 738409基因变异可能增加儿童NAFLD易感性。

Objective To explore the association between variation in genes related to lipid metabolism and the susceptibilityof nonalcoholic fatty liver disease(NAFLD).Methods Obese children with fatty liver aged6~18years old were included.All ofthem got ultrasonic testing,routine examination and biochemical detection.In addition,the DNA of peripheral blood was extractedand the36target genes related to lipid metabolism were detected by next generation sequencing.Results In368obese childrenwho met the inclusion criteria,183children(49.7%)were detected to have NAFL.100children with NAFLD and100childrenwithout 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 wereall higher than those in non-NAFLD children,and there were significant differences(P all<0.05).However,the levels of aspartateaminotransferase(AST),alkaline phosphatase(ALP),apolipoprotein A1(ApoA1),fasting blood glucose,insulin,high densitylipoprotein(HDL),free fatty acid(FFA)and insulin resistance index(HOMA-IR)were not significantly different between the twogroups(P all>0.05).The levels of bilirubine in the two groups were within normal range.Logistic regression analysis showed thatthe 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 encodemicrosomal triglyceride transfer protein(MTTP or MTP),and the mutation of rs738409(OR=2.11,95%CI:1.31~4.48)in genePNPLA3that encode patatin-like phospholipase domain-containing protein3are the independent risk factors for the occurrence ofthe disease.Conclusion Genovariation of MTTP rs2306986,MTTP rs3792683,and PNPLA3rs738409may increase susceptibilityto NAFLD in children.