NOS1AP基因rs12742393位点多态性对瑞格列奈治疗我国汉族2型糖尿病患者疗效的影响  

Effects of NOS1AP rs12742393 Polymorphism on Therapeutic Efficacy of Repaglinide in the Treatment of Type 2 Diabetes Mellitus in Chinese Han Patients

作　　者：王涛 鲁茜 高杏 李伟 吕冬梅 WANG Tao;LU Qian;GAO Xing;LI Wei;LYU Dongmei(Dept. of Pharmacy,the Affiliated Hospital ofXuzhou Medical University,Jiangsu Xuzhou 221002,China;Jiangsu Key Lab of New Drug Research andClinical Pharmacy,Jiangsu Xuzhou 221004,China;Dept. of Endocrinology,the Affiliated Hospital ofXuzhou Medical University,Jiangsu Xuzhou 221002,China)

机构地区：[1]徐州医科大学附属医院药学部,江苏徐州221002 [2]江苏省新药研究与临床药学重点实验室,江苏徐州221004 [3]徐州医科大学附属医院内分泌科,江苏徐州221002

出　　处：《中国药房》2018年第10期1347-1352,共6页China Pharmacy

基　　金：江苏省药学会-百特生物药学基金科研项目(No.201537);徐州市科技项目(No.KC15SH005)

摘　　要：目的:探讨一氧化碳合成酶1调节蛋白(NOS1AP)基因rs12742393位点多态性对瑞格列奈治疗我国汉族2型糖尿病(T2DM)患者疗效的影响。方法:选取2015年8月-2017年3月于徐州医科大学附属医院初诊为T2DM且未接受过任何降糖治疗的汉族患者100例,在常规治疗的基础上加用瑞格列奈片1.0 mg,tid,连续治疗至少8周。采用聚合酶链反应-限制性片断长度多态性法检测患者NOS1AP基因rs12742393位点的基因型,并观察其治疗前后空腹血糖(FPG)、餐后血糖(PPG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、餐后胰岛素(PINS)、胰岛素抵抗指数(HOMA-IR)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇水平。结果:退出和失访的患者各有1例,共有98例患者完成本研究。NOS1AP基因rs12742393位点AA、AC、CC型患者分别有39、42、17例,分布频率分别为39.8%、42.9%、17.3%,均符合Hardy-Weinberg平衡(P>0.05)。治疗8周后,所有患者的FPG、PPG、HbA1c、HOMA-IR、TC、TG水平较治疗前显著下降,FINS、PINS水平较治疗前显著升高,差异均有统计学意义(P<0.05)。治疗前,各基因型患者各项临床指标比较,差异均无统计学意义(P>0.05)。治疗后,各基因型患者FPG、PPG、HbA1c水平,AA型患者HOMA-IR水平,CC型患者TC水平,AA、CC型患者TG水平均较治疗前显著下降;各基因型患者PINS水平,AC、CC型患者FINS水平,CC型患者HOMA-IR水平均较治疗前显著升高;CC型患者FPG、PPG水平显著高于AA、AC型患者,其较治疗前的下降值显著小于AA、AC型患者;AC型患者FPG水平显著高于AA型;AC、CC型患者FINS水平及较治疗前的上升值、HOMA-IR水平均显著高于或大于AA型,各基因型患者HOMA-IR较治疗前的变化值两两比较,差异均有统计学意义(P<0.05)。而其余指标在治疗前后、组间比较差异均无统计学意义(P>0.05)。结论:NOS1AP基因rs12742393位点多态性可能影响瑞格列奈治疗我国汉族TOBJECTIVE：To investigate the effects of NOS1AP rs12742393 polymorphism on therapeutic efficacy of repaglinidein the treatment of type 2 diabetes mellitus（T2DM）in Chinese Han patients. METHODS：A total of 100 newly-diagnosed T2DMHan patients without any hypoglycemic therapy were selected from the Affiliated Hospital of Xuzhou Medical University duringAug. 2015-Mar. 2017. Based on routine therapy,they were additionally given Repaglinide tablets 1.0 mg,tid,for consecutive 8weeks at least. PCR-RFLP was used to detect the genotypes at NOS1AP rs12742393 in patients. The levels of FPG,PPG,HbA1c,FINS,PINS,HOMA-IR,TC,TG,HDL-C and LDL-C were observed before and after treatment. RESULTS：There were 1 caseof withdrawal and 1 case of follow-up loss,and 98 patients accomplished the study. There were 39 cases of NOS1AP rs12742393AA genotype,42 cases of AC genotype and 17 cases of CC genotype,the frequency of them were 39.8%,42.9%,17.3%,whichwere in line with Hardy-Weinberg equilibrium（P〉0.05）. After 8 weeks,the levels of FPG,PPG,HbA1c,HOMA-IR,TC andTG were decreased significantly,compared with before treatment;the levels of FINS and PINS were increased significantly,compared with before treatment,with statistical significance（P〈0.05）. Before treatment,there was no statistical significance ineach index among different genotypes（P〉0.05）. After treatment,the levels of FPG,PPG and HbA1c in all genotypes,the levelof HOMA-IR in AA genotypes,the level of TC in CC genotype,the level of TG in AA and CC genotype were decreasedsignificantly;the level of PINS in all genotype,the level of FINS in AC and CC genotype and the level of HOMA-IR in CCgenotype were increased significantly;the levels of FPG and PPG in CC genotype were significantly higher than AA and ACgenotype,and the decrease of two indexes than before treatment were significantly less than AA and AC genotype;the level ofFPG in AC genotype was significantly higher than AA genotype;the level and increase than before treatment of FINS,and thelevel of HOMA-

关 键 词：NOS1AP基因 rs12742393位点 基因多态性 2型糖尿病 汉族 瑞格列奈 疗效 血糖 血脂 胰岛素 

分 类 号：R969.3[医药卫生—药理学] R587.1[医药卫生—药学]