【摘要】 目的 探讨三明地区糖尿病儿童的易感基因,加深对儿童糖尿病病因及发病机制的认识,为精准治疗提供依据。方法 方便选取2020年1月—2024年12月在三明市第一医院接受治疗的350例糖尿病患儿作为研究组,另选取同期350例在本院进行健康体检的儿童作为对照组。收集两组研究对象一般资料并进行体格检查。参考已发表的文献及相关研究成果,选定糖代谢途径涉及的125个基因作为目标基因。主要包括单基因糖尿病相关基因、1型和2型糖尿病易感性相关基因、家族性高胰岛素低血糖症相关基因。采集血标本提取DNA,利用高通量测序及Sanger测序相结合的方式,筛查儿童糖尿病的致病基因。分析基因变异与糖尿病类型的关联。结果 研究组Wolfram综合征1基因(wolfram syndrome 1 gene, WFS1)、肝细胞核因子1α(hepatocyte nuclear factor 1 alpha, HNF1A)、钾电压门控通道亚家族J成员(potassium voltage-gated channel subfamily J member 11, KCNJ11)、人类白细胞抗原-DQA1(human leukocyte antigen-DQA1, HLA-DQA1)基因变异率均高于对照组,差异均有统计学意义(P均<0.05)。关联分析显示HNF1A与青少年成人型糖尿病相关,KCNJ11与新生儿糖尿病有关,DQA1基因与1型糖尿病有关,WFS1基因与2型糖尿病有关(P均<0.05)。结论 多种基因在糖尿病儿童中均发生改变,提示这些基因可能在三明地区儿童糖尿病的发生和发展过程中发挥重要作用。更多还原

【Abstract】 Objective To explore the susceptibility genes of children with diabetes in Sanming area, to deepen the understanding of the etiology and pathogenesis of diabetes mellitus in children, and to provide the basis for precise treatment. Methods A total of 350 children with diabetes mellitus who were treated in Sanming First Hospital from January 2020 to December 2024 were conveniently selected as the study group, and 350 children who underwent physical examination in the hospital during the same period were selected as the control group. The general data of the two groups of subjects were collected and physical examinations were performed. Referring to the published literature and related research results, 125 genes involved in the glucose metabolism pathway were selected as the target genes. It mainly includes single gene diabetes-related genes, type 1 and type 2 diabetes susceptibility-related genes, and familial hyperinsulinemic hypoglycemia-related genes. Blood samples were collected to extract DNA, and high-throughput sequencing and Sanger sequencing were used to screen the pathogenic genes of diabetes mellitus in children. The association between gene variation and type of diabetes mellitus was analyzed. Results The mutation rates of wolfram syndrome 1 gene(WFS1), hepatocyte nuclear factor 1 alpha(HNF1A), potassium voltage-gated channel subfamily J member 11(KCNJ11) and human leukocyte antigen-DQA1(HLA-DQA1) in the study group were higher than those in the control group, the differences were statistically significant(all P<0.05). Correlation analysis showed that HNF1A was associated with maturity-onset diabetes of the young, KCNJ11 was associated with neonatal diabetes mellitus, DQA1 gene was associated with type 1 diabetes mellitus, and WFS1 gene was associated with type 2 diabetes mellitus(all P<0.05). Conclusion Many genes are changed in children with diabetes, suggesting that these genes may play an important role in the occurrence and development of diabetes in children in Sanming area.更多还原