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
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篇名: 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
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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T2DM患者的疗效,其风险基因C可能通过影响患者的FPG、PPG、FINS和HOMA-IR水平来降低瑞格列奈的疗效。
ABSTRACT: OBJECTIVE: To investigate the effects of NOS1AP rs12742393 polymorphism on therapeutic efficacy of repaglinide in the treatment of type 2 diabetes mellitus (T2DM) in Chinese Han patients. METHODS: A total of 100 newly-diagnosed T2DM Han patients without any hypoglycemic therapy were selected from the Affiliated Hospital of Xuzhou Medical University during Aug. 2015-Mar. 2017. Based on routine therapy, they were additionally given Repaglinide tablets 1.0 mg, tid, for consecutive 8 weeks 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 case of withdrawal and 1 case of follow-up loss, and 98 patients accomplished the study. There were 39 cases of NOS1AP rs12742393 AA genotype, 42 cases of AC genotype and 17 cases of CC genotype, the frequency of them were 39.8%, 42.9%, 17.3%, which were in line with Hardy-Weinberg equilibrium (P>0.05). After 8 weeks, the levels of FPG, PPG, HbA1c, HOMA-IR, TC and TG 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 in each index among different genotypes (P>0.05). After treatment, the levels of FPG, PPG and HbA1c in all genotypes, the level of HOMA-IR in AA genotypes, the level of TC in CC genotype, the level of TG in AA and CC genotype were decreased significantly; the level of PINS in all genotype, the level of FINS in AC and CC genotype and the level of HOMA-IR in CC genotype were increased significantly; the levels of FPG and PPG in CC genotype were significantly higher than AA and AC genotype, and the decrease of two indexes than before treatment were significantly less than AA and AC genotype; the level of FPG in AC genotype was significantly higher than AA genotype; the level and increase than before treatment of FINS, and the level of HOMA-IR in AC and CC genotype was significantly higher than AA genotype; there was statistical significance in the change than before treatment of HOMA-IR among all genotypes (P<0.05). There was no statistical significance in other indexes among all groups before and after treatment(P>0.05). CONCLUSIONS: NOS1AP rs12742393 polymorphism may influence therapeutic efficacy of repaglinide in the treatment of T2DM in Chinese Han patients, and risk gene C may weaken therapeutic efficacy of repaglinide by influencing the levels of FPG, PPG, FINS and HOMA-IR.
期刊: 2018年第29卷第10期
作者: 王涛,鲁茜,高杏,李伟,吕冬梅
AUTHORS: WANG Tao,LU Qian,GAO Xing,LI Wei,LYU Dongmei
关键字: 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
KEYWORDS: NOS1AP gene; rs12742393; Gene polymorphism; Type 2 diabetes mellitus; Han population; Repaglinide; Therapeutic efficacy; Blood glucose; Blood lipid; Insulin
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