DDAH基因多态性影响格列苯脲治疗妊娠期糖尿病效果及其相关性分析  

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

作　　者：李睿 王红红 郭慧涛 LI Rui;WANG Hong-hong;GUO Hui-tao(Department of Obstetrics,Shanxi Provincial Children’s Hospital,Maternal and Child Health Hospital,Taiyuan 030013,China)

机构地区：[1]山西省儿童医院妇幼保健院产科,山西太原030013

出　　处：《中国药物应用与监测》2023年第5期330-333,共4页Chinese Journal of Drug Application and Monitoring

摘　　要：目的:探讨DDAH基因多态性对格列苯脲治疗妊娠期糖尿病(Gestational diabetes mellitus,GDM)疗效的影响及其与人类软骨糖蛋白-39(YKL-40)、视黄醇结合蛋白4(Retinol binding protein,RBP4)水平的相关性研究。方法:选择山西省儿童医院妇幼保健院于2019年1月至2022年1月收治的346例GDM患者为研究对象,根据DDAH rs1241321位点基因多态性分为AA基因型组、AG基因型组及GG基因型组。三组患者给予格列本脲联合门冬胰岛素治疗8周后对比三组患者的血糖指标、临床疗效及治疗前后血清YKL-40、RBP4表达水平差异;并通过相对风险度(OR)分析DDAH1基因与格列苯脲降糖效应之间的相关性。结果:格列本脲联合门冬胰岛素治疗后,AA基因型组餐后血糖指标2-hPG、HOMA-IR、FPG与血清YKL-40、RBP4浓度均高于GG基因型组、AG基因型组,且AG基因型组高于GG基因型组,差异具有统计学意义(P<0.001)。相对风险度(OR)分析结果显示DDAH1基因rs1241321位点基因型(AA、AG、GG)与YKL-40、RBP4下降水平之间存在显著相关性(OR=0.516,95%CI=0.262~0.846,P=0.012;OR=0.456,95%CI=0.184~0.827,P=0.023)。结论:DDAH基因多态性可能通过内皮一氧化氮合酶(NOS)/DDAH通路改善胰岛素敏感性,影响血清YKL-40、RBP4表达水平,导致格列本脲联合门冬胰岛素治疗GDM在降糖效果及临床疗效上存在差异。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.

关 键 词：基因多态性 格列苯脲 妊娠糖尿病 软骨糖蛋白-39 视黄醇结合蛋白4 

分 类 号：R714.256[医药卫生—妇产科学]