脂肪细胞因子通路基因多态性与肥胖儿童非酒精性脂肪性肝病的关联  

Association of adipocytokine pathway gene polymorphisms with NAFLD in obese children

作　　者：王洁 潘雄峰 韦佳 李雄伟 周海湘 徐宁安[3] 康如彤[3] 钟燕[3] 罗家有 WANG Jie;PAN Xiongfeng;WEI Jia;LI Xiongwei;ZHOU Haixiang;XU Ning’an;KANG Rutong;ZHONG Yan;LUO Jiayou(Department of Maternal and Child Health,Xiangya School of Public Health,Central South University,Changsha 410013;Center for Disease Control and Prevention of Ningxiang City,Changsha 410699;Child Health Care Centre,Hunan Children’s Hospital,Changsha 410007,China)

机构地区：[1]中南大学湘雅公共卫生学院儿少卫生与妇幼保健学系,长沙410013 [2]宁乡市疾病预防控制中心,长沙410699 [3]湖南省儿童医院儿童保健所,长沙410007

出　　处：《中南大学学报（医学版）》2024年第5期775-783,共9页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(81872641);湖南省自然科学基金(2021JJ30901)。

摘　　要：目的:非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)存在明显的遗传易感性,脂肪细胞因子通过参与胰岛素抵抗和肝脏脂肪变性等过程,在NAFLD的发生和发展中发挥重要作用,但参与脂肪细胞因子通路的基因与NAFLD之间的关联仍不明确。本研究旨在探索脂肪细胞因子通路的基因多态性位点及其交互作用与肥胖儿童NAFLD的关联。方法:采用病例对照研究,将肥胖儿童分为NAFLD组和对照组。采集受试者外周静脉血2 mL,提取DNA后采用多重PCR和高通量测序对脂肪细胞因子通路的14个单核苷酸多态性(single nucleotide polymorphism,SNP)进行分型检测。采用单因素及多因素Logistic回归分析各SNP与肥胖儿童NAFLD的关联。基于显性模型,联合使用交叉分析和Logistic回归分析相加或相乘交互作用。采用广义多因子降维法(generalized multifactor dimensionality reduction,GMDR)检测14个SNP之间基因-基因交互作用与肥胖儿童NAFLD之间的关联。结果:共纳入1 022例儿童,NAFLD组与对照组各511例。在调整年龄、性别、BMI后,多因素Logistic回归结果显示:PPARG rs1801282在3个遗传模型中与肥胖儿童NAFLD存在关联,分别是杂合子模型(CG vs CC,OR=0.58,95%CI 0.36~0.95,P=0.029)、显性模型(CG+GG vs CC,OR=0.62,95%CI 0.38~1.00,P=0.049)、超显性模型(CC+GG vs CG,OR=1.72,95%CI 1.06~2.80,P=0.028);PRKAG2 rs12703159在4个遗传模型中与肥胖儿童NAFLD存在关联,分别是杂合子模型(CT vs CC,OR=1.51,95%CI 1.10~2.07,P=0.011)、显性模型(CT+TT vs CC,OR=1.50,95%CI 1.10~2.03,P=0.010)、超显性模型(CC+TT vs CT,OR=0.67,95%CI 0.49~0.92,P=0.012)、加性模型(CC vs CT vs TT,OR=1.40,95%CI 1.07~1.83,P=0.015)。但PPARG rs1801282与PRKAG2 rs12703159间的相乘及相加交互作用均与肥胖儿童NAFLD不存在关联。经GMDR分析,调整年龄、性别、BMI后,14个SNP之间的交互作用均无统计学意义(均P>0.05)。结论:PPARG rs1801282、PRKAG2 rs12703159突变型与肥胖Objective:Non-alcoholic fatty liver disease(NAFLD)has significant genetic susceptibility.Adipocytokines play a crucial role in NAFLD development by participating in insulin resistance and hepatic steatosis.However,the association between adipocytokine pathway genes and NAFLD remains unclear.This study aims to explore the association of gene polymorphisms in the adipocytokine pathway and their interactions with NAFLD in obese children.Methods:A case-control study was conducted,dividing obese children into NAFLD and control groups.Peripheral venous blood(2 mL)was collected from each participant for DNA extraction.A total of 14 single nucleotide polymorphisms(SNP)in the adipocytokine pathway were genotyped using multiplex PCR and high-throughput sequencing.Univariate and multivariate Logistic regression analyses were used to assess the association between SNP and NAFLD in obese children.Dominant models were used to analyze additive and multiplicative interactions via crossover analysis and Logistic regression.Generalized multifactor dimensionality reduction(GMDR)was used to detect gene-gene interactions among the 14 SNPs and their association with NAFLD in obese children.Results:A total of 1022 children were included,with 511 in the NAFLD group and 511 in the control group.After adjusting for age,gender,and BMI,multivariate Logistic regression showed that PPARG rs1801282 was associated with NAFLD in the obese children in 3 genetic models:heterozygote model(CG vs CC,OR=0.58,95%CI 0.36 to 0.95,P=0.029),dominant model(GG+CG vs CC,OR=0.62,95%CI 0.38 to 1.00,P=0.049),and overdominant model(CC+GG vs CG,OR=1.72,95%CI 1.06 to 2.80,P=0.028).PRKAG2 rs12703159 was associated with NAFLD in 4 genetic models:heterozygous model(CT vs CC,OR=1.51,95%CI 1.10 to 2.07,P=0.011),dominant model(CT+TT vs CC,OR=1.50,95%CI 1.10 to 2.03,P=0.010),overdominant model(CC+TT vs CT,OR=0.67,95%CI 0.49 to 0.92,P=0.012),and additive model(CC vs CT vs TT,OR=1.40,95%CI 1.07 to 1.83,P=0.015).No significant multiplicative or additive interaction between P

关 键 词：肥胖儿童 非酒精性脂肪性肝病 脂肪细胞因子 单核苷酸多态性 交互作用 广义多因子降维法 

分 类 号：R723.14[医药卫生—儿科] R725.7[医药卫生—临床医学]