Effect of DDAH gene polymorphism on efficacy of glibenclamide in treatment of GDM and its correlation with YKL-40 and RBP4 levels

LI Rui; WANG Hong-hong; GUO Hui-tao

doi:10.3969/j.issn.1672-8157.2023.05.013

Abstract：Objective:To investigate the effect of DDAH gene polymorphism on the efficacy of glibenclamide in the treatment of gestational diabetes mellitus(Gestational diabetes mellitus,GDM)and its relationship with human cartilage glycoprotein-39(YKL-40)and retinol binding protein 4(Retinol binding protein,RBP4)level.Methods:346 invalids with GDM admitted to our hospital were selected as the research subjects,according to the results of the rs1241321 locus of DDAH gene polymorphism detection,they were divided into AA genotype group,AG genotype group and GG genotype group.The three groups of patients were treated with glibenclamide combined with insulin aspart for 8 consecutive weeks.The changes of blood glucose index,clinical treatment efficacy and the difference of serum YKL-40 and RBP4 expression levels before and after treatment in the three groups of patients with different genotypes were compared.The relative risk(OR)was used to analyze the correlation between the rs1241321 locus of DDAH1 gene and the hypoglycemic effect of glibenclamide.Results:After treatment with glibenclamide combined with insulin,postprandial blood glucose index 2-hPG,HOMA-IR,FPG and the serum YKL-40,RBP4 levels in the AA genotype group were obvious higher than in AG genotype group and the GG genotype group,and the levels of the above indicators in the AG genotype group were higher than in GG genotype group(P<0.05).Relative risk(OR)analysis results showed that there was a significant correlation between the genotypes(GG,AG,AA)at rs1241321 locus of DDAH1 gene and the decline levels of YKL-40 and RBP4(OR = 0.516,95%CI = 0.262-0.846,P = 0.012;OR = 0.456,95%CI = 0.184-0.827,P = 0.023).Conclusion:DDAH gene polymorphism may improve insulin sensitivity by affecting the endothelial nitric oxide synthase(NOS)/DDAH pathway,and the serum YKL-40 and RBP4 expression levels,which leads to differences in the hypoglycemic effect and clinical treatment of glibenclamide combined with insulin in patients with GDM.