PPARG基因rs1801282位点多态性与2型糖尿病视网膜病变的相关性

Association of Rs1801282 Polymorphisms in PPARG Gene with Diabetic Retinopathy in Type 2 Diabetes Mellitus

目的研究PPARG基因rs1801282位点基因多态性与2型糖尿病视网膜病变(type 2 diabetic retinopathy,T2DR)的相关性。探讨PPARG基因参与T2DR发生发展的机制。方法收集2型糖尿病(type 2 diabetes mellitus,T2DM)患者,根据眼底病变情况分为糖尿病视网膜病变[DR(+)]组和无糖尿病视网膜病变[DR(-)]组。收集患者年龄、性别、病程等一般情况及血糖、血脂、C肽等临床指标。检测两组患者外周血PPARG基因rs1801282位点基因型,比较两组PPARG基因型及等位基因的分布情况,分析PPARG基因rs1801282位点与T2DR的相关性以及PPARG基因转录物在T2DR发生发展中的机制。结果纳入T2DM患者27例,两组患者性别、年龄、收缩压、舒张压及体重指数比较均无统计学差异(P>0.05),病程比较差异有统计学意义(P<0.05)。[DR(+)]组PPARG基因rs1801282位点等位基因型有G/C和C/C两种,而DR(-)组的均为C/C,两组PPARG基因rs1801282位点等位基因分布数量比较差异有统计学意义(P<0.05)。使用miRTarBase数据库、Targetscan、miRDB数据库预测靶向PPARG的miRNA,对这4个miRNA进行靶基因预测分析,取交集得到105个靶基因,进行GO功能富集分析、KEGG通路富集分析提示PPARG可能参与细菌侵袭上皮细胞、AMPK信号通路、破骨细胞分化、粘合连接及PI3K-Akt等信号通路。利用String数据库验证PPARG与相关蛋白作用及可能参与的信号通路有甲状腺激素信号通路、AMPK信号通路、胰高血糖素信号通路、粘合连接等。结论PPARG基因rs1801282等位基因型G/C可能是T2DR预测因子。hsa-miR-27b-3p、hsa-miR-130a-3p、hsa-miR-130b-3p、hsa-miR-27a-3p等4个miRNA可能靶向PPARG参与AMPK信号通路及粘合连接信号通路调控T2DR的发生发展。

Objective To investigate the association between PPARG polymorphisms at rs1801282 and type 2 diabetic retinopathy(T2DR)and explore the mechanism of PPARG gene involved in the development of T2DR.Methods Patients with type 2 diabetes mellitus(T2DM)were divided into diabetic retinopathy[DR(+)]group and diabetic retinopathy DR(-)group according to fundus lesions.The patients′age,gender,course of disease,blood glucose,blood lipid,C-peptide and other clinical indicators were collected.The genotype of PPARG gene rs1801282 in peripheral blood of the two groups was detected,and the distribution of PPARG genotype and allele was compared between the two groups.The correlation between PPARG gene rs1801282 and T2DR and the mechanism of PPARG gene transcript in the occurrence and development of T2DR were analyzed.Results A total of 27 patients with T2DM were included.There were no significant differences in gender,age,systolic blood pressure,diastolic blood pressure and body mass index between the two groups(P>0.05),and there was a significant difference in the course of disease between the two groups(P<0.05).The DR(+)group had G/C and C/C alleles of PPARG gene rs1801282,while the DR(-)group had C/C alleles.There was a significant difference in the number of allele distributions of PPARG gene rs1801282 between the two groups(P<0.05).MiRTarBase database,Targetscan database and miRDB database were used to predict the mirnas targeting PPARG.Target gene prediction analysis was performed on these four mirnas,and 105 target genes were obtained by intersection.GO functional enrichment analysis and KEGG pathway enrichment analysis suggested that PPARG might be involved in bacterial invasion of epithelial cells,AMPK signaling pathway,osteoclast differentiation,adhesion and PI3K-Akt signaling pathway.String database was used to verify the role of PPARG and related proteins and the possible involved signaling pathways were thyroid hormone signaling pathway,AMPK signaling pathway,glucagon signaling pathway,adhesive connection,etc.Conclusion PPARG rs1801282 G/C allele may be a predictor of T2DR.Four mirnas including hsa-miR-27b-3p,hsa-miR-130a-3p,hsa-miR-130b-3p and hsa-miR-27a-3p may target PPARG and participate in AMPK signaling pathway and adhesive junction signaling pathway to regulate the occurrence and development of T2DR.