PDF(Pubmed)
Abstract：
OBJECTIVE: Insulin signaling pathway plays an important role in metabolic associated fatty liver disease (MAFLD), however, the association between polymorphisms of genes related to insulin signaling pathway and MAFLD remains unclear. This study aims to investigate the association between insulin signaling pathway-related gene polymorphisms and gene-gene interactions with MAFLD susceptibility in obese children so as to provide scientific basis for further study of genetic mechanism.
METHODS: A total of 502 obese children with MAFLD who admitted to Hunan Provincial Children\'s Hospital from September 2019 to October 2021, were recruited as a case group, and 421 obese children with non-MAFLD admitted during the same period were recruited as a control group. Socio-demographic information, preterm birth history, eating habits, and exercise status of the subjects were collected by inquiry survey, and anthropometric information was collected by physical measurement. At the same time, 2 mL of venous blood was collected to extract DNA, and the polymorphism of insulin signaling pathway-related genes (5 representative candidate genes, 12 variants) was detected. Multivariate Logistic regression analysis was used to investigate the association between insulin signaling pathway-related gene polymorphisms and MAFLD in obese children.
RESULTS: After adjusting for confounder factors, INS rs3842748 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 1.749 (1.053 to 2.905), 1.909 (1.115 to 3.267), 1.862 (1.098 to 3.157), all P<0.05]; INS rs3842752 was significantly associated with the risk of MAFLD in obese children in heterozygous and dominant models [OR and 95% CI 1.736 (1.028 to 2.932), 1.700 (1.015 to 2.846), all P<0.05]. NR1H3 rs3758674 was significantly correlated with the risk of MAFLD in obese children in allele model [OR and 95% CI 0.716 (0.514 to 0.997), P<0.05]. SREBP-1c rs2297508 was significantly associated with the risk of MAFLD in obese children in allele and dominant models [OR and 95% CI 0.772 (0.602 to 0.991) and 0.743 (0.557 to 0.991), all P<0.05]. SREBP-1c rs8066560 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 0.759 (0.589 to 0.980), 0.733 (0.541 to 0.992), 0.727 (0.543 to 0.974), all P<0.05]. NR1H3 rs3758674 mutant C and SREBP-1c rs2297508 mutant G had interaction in the development of MAFLD in obese children [OR and 95% CI 0.407 (0.173 to 0.954), P<0.05].
CONCLUSIONS: The INS, NR1H3, and SREBP-1c gene polymorphisms in the insulin signaling pathway are associated with the susceptibility of MAFLD in obese children, but the functions and mechanisms of these genes need to be further studied.
目的: 胰岛素信号通路在代谢相关脂肪性肝病(metabolic associated fatty liver disease，MAFLD)的发生、发展中具有重要作用，但该通路相关基因多态性与MAFLD的关联尚不明确。本研究旨在探讨胰岛素信号通路相关基因多态性和基因-基因交互作用与肥胖儿童MAFLD易感性的关联，为后续遗传机制的研究提供科学依据。方法: 招募2019年9月至2021年10月在湖南省儿童医院就诊的502例肥胖儿童MAFLD患者为病例组，以同期就诊的421例肥胖儿童非MAFLD患者为对照组。采用调查问卷收集研究对象社会人口学信息、早产史、饮食习惯、运动情况，体格检查收集人体测量学数据；同时，采集静脉血2 mL提取DNA，检测胰岛素信号通路相关基因多态性(5个代表性候选基因、12个位点)；采用多因素Logistic回归分析探讨胰岛素信号通路基因多态性与肥胖儿童MAFLD的关联。结果: 调整混杂因素后，INS rs3842748在等位基因、杂合子和显性模型下与肥胖儿童MAFLD风险显著相关[OR及95% CI分别为1.749(1.053~2.905)、1.909(1.115~3.267)、1.862(1.098~3.157)，均P<0.05]；INS rs3842752在杂合子和显性模型下与肥胖儿童MAFLD风险显著相关[OR及95% CI分别为1.736(1.028~2.932)、1.700(1.015~2.846)，均P<0.05]；NR1H3 rs3758674在等位基因模型下与肥胖儿童MAFLD风险显著相关[OR及95% CI为0.716(0.514~0.997)， P<0.05]；SREBP-1c rs2297508在等位基因和显性模型下与肥胖儿童MAFLD风险显著相关[OR及95% CI分别为0.772(0.602~0.991)、0.743(0.557~0.991)，均P<0.05]；SREBP-1c rs8066560在等位基因、杂合子、显性模型下与肥胖儿童MAFLD风险显著相关[OR及95% CI分别为0.759(0.589~0.980)、0.733(0.541~0.992)、0.727(0.543~0.974)，均P<0.05]。NR1H3 rs3758674突变体C与SREBP-1c rs2297508突变体G在肥胖儿童MAFLD发生中存在交互作用[OR及95% CI为0.407(0.173~0.954)，P<0.05]。结论: 胰岛素信号通路中INS、NR1H3、SREBP-1c基因多态性与肥胖儿童MAFLD易感性存在关联，但上述基因的功能及其作用机制有待进一步研究。.
METHODS: A total of 502 obese children with MAFLD who admitted to Hunan Provincial Children\'s Hospital from September 2019 to October 2021, were recruited as a case group, and 421 obese children with non-MAFLD admitted during the same period were recruited as a control group. Socio-demographic information, preterm birth history, eating habits, and exercise status of the subjects were collected by inquiry survey, and anthropometric information was collected by physical measurement. At the same time, 2 mL of venous blood was collected to extract DNA, and the polymorphism of insulin signaling pathway-related genes (5 representative candidate genes, 12 variants) was detected. Multivariate Logistic regression analysis was used to investigate the association between insulin signaling pathway-related gene polymorphisms and MAFLD in obese children.
RESULTS: After adjusting for confounder factors, INS rs3842748 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 1.749 (1.053 to 2.905), 1.909 (1.115 to 3.267), 1.862 (1.098 to 3.157), all P<0.05]; INS rs3842752 was significantly associated with the risk of MAFLD in obese children in heterozygous and dominant models [OR and 95% CI 1.736 (1.028 to 2.932), 1.700 (1.015 to 2.846), all P<0.05]. NR1H3 rs3758674 was significantly correlated with the risk of MAFLD in obese children in allele model [OR and 95% CI 0.716 (0.514 to 0.997), P<0.05]. SREBP-1c rs2297508 was significantly associated with the risk of MAFLD in obese children in allele and dominant models [OR and 95% CI 0.772 (0.602 to 0.991) and 0.743 (0.557 to 0.991), all P<0.05]. SREBP-1c rs8066560 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 0.759 (0.589 to 0.980), 0.733 (0.541 to 0.992), 0.727 (0.543 to 0.974), all P<0.05]. NR1H3 rs3758674 mutant C and SREBP-1c rs2297508 mutant G had interaction in the development of MAFLD in obese children [OR and 95% CI 0.407 (0.173 to 0.954), P<0.05].
CONCLUSIONS: The INS, NR1H3, and SREBP-1c gene polymorphisms in the insulin signaling pathway are associated with the susceptibility of MAFLD in obese children, but the functions and mechanisms of these genes need to be further studied.
目的: 胰岛素信号通路在代谢相关脂肪性肝病(metabolic associated fatty liver disease，MAFLD)的发生、发展中具有重要作用，但该通路相关基因多态性与MAFLD的关联尚不明确。本研究旨在探讨胰岛素信号通路相关基因多态性和基因-基因交互作用与肥胖儿童MAFLD易感性的关联，为后续遗传机制的研究提供科学依据。方法: 招募2019年9月至2021年10月在湖南省儿童医院就诊的502例肥胖儿童MAFLD患者为病例组，以同期就诊的421例肥胖儿童非MAFLD患者为对照组。采用调查问卷收集研究对象社会人口学信息、早产史、饮食习惯、运动情况，体格检查收集人体测量学数据；同时，采集静脉血2 mL提取DNA，检测胰岛素信号通路相关基因多态性(5个代表性候选基因、12个位点)；采用多因素Logistic回归分析探讨胰岛素信号通路基因多态性与肥胖儿童MAFLD的关联。结果: 调整混杂因素后，INS rs3842748在等位基因、杂合子和显性模型下与肥胖儿童MAFLD风险显著相关[OR及95% CI分别为1.749(1.053~2.905)、1.909(1.115~3.267)、1.862(1.098~3.157)，均P<0.05]；INS rs3842752在杂合子和显性模型下与肥胖儿童MAFLD风险显著相关[OR及95% CI分别为1.736(1.028~2.932)、1.700(1.015~2.846)，均P<0.05]；NR1H3 rs3758674在等位基因模型下与肥胖儿童MAFLD风险显著相关[OR及95% CI为0.716(0.514~0.997)， P<0.05]；SREBP-1c rs2297508在等位基因和显性模型下与肥胖儿童MAFLD风险显著相关[OR及95% CI分别为0.772(0.602~0.991)、0.743(0.557~0.991)，均P<0.05]；SREBP-1c rs8066560在等位基因、杂合子、显性模型下与肥胖儿童MAFLD风险显著相关[OR及95% CI分别为0.759(0.589~0.980)、0.733(0.541~0.992)、0.727(0.543~0.974)，均P<0.05]。NR1H3 rs3758674突变体C与SREBP-1c rs2297508突变体G在肥胖儿童MAFLD发生中存在交互作用[OR及95% CI为0.407(0.173~0.954)，P<0.05]。结论: 胰岛素信号通路中INS、NR1H3、SREBP-1c基因多态性与肥胖儿童MAFLD易感性存在关联，但上述基因的功能及其作用机制有待进一步研究。.
摘要：
暂无翻译
