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.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2024 May 28;49(5):775-783. doi: 10.11817/j.issn.1672-7347.2024.230098.
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.
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.
A total of 1 022 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 rs1801282 was associated with NAFLD in the obese children in 3 genetic models: heterozygote model (CG vs CC, =0.58, 95% 0.36 to 0.95, =0.029), dominant model (GG+CG vs CC, =0.62, 95% 0.38 to 1.00, =0.049), and overdominant model (CC+GG vs CG, =1.72, 95% 1.06 to 2.80, =0.028). rs12703159 was associated with NAFLD in 4 genetic models: heterozygous model (CT vs CC, =1.51, 95% 1.10 to 2.07, =0.011), dominant model (CT+TT vs CC, =1.50, 95% 1.10 to 2.03, =0.010), overdominant model (CC+TT vs CT, =0.67, 95% 0.49 to 0.92, =0.012), and additive model (CC vs CT vs TT, =1.40, 95% 1.07 to 1.83, =0.015). No significant multiplicative or additive interaction between rs1801282 and rs12703159 was found in association with NAFLD. GMDR analysis, adjusted for age, gender, and BMI, revealed no statistically significant interactions among the 14 SNPs (all >0.05).
Mutations in rs1801282 and rs12703159 are associated with NAFLD in obese children. However, no gene-gene interactions among the SNP are found to be associated with NAFLD in obese children.
非酒精性脂肪性肝病（NAFLD）具有显著的遗传易感性。脂肪细胞因子在胰岛素抵抗和肝脂肪变性中发挥重要作用，参与 NAFLD 的发生发展。然而，脂肪细胞因子通路基因与 NAFLD 之间的关联尚不清楚。本研究旨在探讨肥胖儿童中脂肪细胞因子通路基因多态性及其与 NAFLD 的相关性。
采用病例对照研究，将肥胖儿童分为 NAFLD 组和对照组。采集每位参与者外周静脉血（2mL）用于 DNA 提取。采用多重 PCR 和高通量测序技术对脂肪细胞因子通路中的 14 个单核苷酸多态性（SNP）进行基因分型。采用单因素和多因素 Logistic 回归分析评估 SNP 与肥胖儿童 NAFLD 的相关性。采用交叉分析和 Logistic 回归分析加性和显性模型分析 SNP 之间的相加和相乘交互作用。采用广义多因素维度缩减（GMDR）分析 14 个 SNP 之间的基因-基因相互作用及其与肥胖儿童 NAFLD 的相关性。
共纳入 1022 名儿童，其中 511 名儿童患有 NAFLD，511 名儿童为对照组。在调整年龄、性别和 BMI 后，多因素 Logistic 回归分析显示，rs1801282 在肥胖儿童中与 3 种遗传模型中的 NAFLD 相关：杂合模型（CG 与 CC，=0.58，95%CI：0.36-0.95，=0.029）、显性模型（GG+CG 与 CC，=0.62，95%CI：0.38-1.00，=0.049）和超显性模型（CC+GG 与 CG，=1.72，95%CI：1.06-2.80，=0.028）。rs12703159 与肥胖儿童的 4 种遗传模型相关：杂合模型（CT 与 CC，=1.51，95%CI：1.10-2.07，=0.011）、显性模型（CT+TT 与 CC，=1.50，95%CI：1.10-2.03，=0.010）、超显性模型（CC+TT 与 CT，=0.67，95%CI：0.49-0.92，=0.012）和加性模型（CC 与 CT 与 TT，=1.40，95%CI：1.07-1.83，=0.015）。rs1801282 和 rs12703159 之间未发现与 NAFLD 相关的显著相乘或相加交互作用。经年龄、性别和 BMI 调整后的 GMDR 分析显示，14 个 SNP 之间没有统计学意义的相互作用（均>0.05）。
rs1801282 和 rs12703159 的突变与肥胖儿童的 NAFLD 相关。然而，在肥胖儿童中，没有发现 SNP 之间的基因-基因相互作用与 NAFLD 相关。
