瘦素受体基因Gln223Arg多态性与2型糖尿病合并高尿酸血症患者的关系以及二甲双胍治疗效果的评价

The Relationship Between Gln223Arg Polymorphism of the Leptin Receptor Geneand Patients with Type 2 Diabetes Mellitus Complicated with Hyperuricemia and the Evaluation of the Therapeutic Effect of Metformin

目的评价瘦素受体基因Gln223Arg多态性与2型糖尿病(type 2 diabetes,T2DM)合并高尿酸血症(hyperuricemia,HUA)患者的关系以及二甲双胍治疗效果。方法取2018年3月至2019年12月我院收治的160例初诊T2DM患者,根据T2DM患者是否合并HUA分为T2DM组(n=80)和合并组(n=80)。通过PCR限制性片段长度多态性(PCR-RELP)法测定瘦素(LEP)受体基因Gln223Arg多态性分布频率,并使用多因素非条件Logistic回归对T2DM合并HUA患者的危险因素进行分析,同时对T2DM合并HUA患者进行二甲双胍治疗,分析二甲双胍疗效与各基因型的关系。结果两组性别、年龄、总胆固醇(TC)、高密度脂蛋白(HDL-C)比较,组间差异无统计学意义(P>0.05);合并组吸烟史、冠心病史、糖尿病病程、体质量指数(BMI)、三酰甘油(TG)、低密度脂蛋白(LDL-C)、糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)、尿酸(UA)、LEP均高于T2DM组(P<0.05);T2DM组和合并组瘦素受体Gln223Arg各基因型的期望值和观察值比较,P均>0.05,符合Hardy-Weinberg平衡定律;与T2DM组对比,合并组Gln223Arg基因位点AA型、AG型显著降低(P<0.05),而GG型显著升高(P<0.05);行多因素Logistic回归分析,结果显示,T2DM合并HUA患者基因型GG、吸烟史、冠心病史、糖尿病病程、BMI、TG、LDL-C、HbA1c、HOMA-IR、尿酸、LEP是危险因素;GG型、AG型FPG、2hPBG、HbA1降低幅度均低于AA型(P<0.05),而GG型FPG、2hPBG、HbA1降低幅度均低于AG型(P<0.05)。结论T2DM患者携带GG基因型可能是HUA的易感因素,且瘦素受体基因Gln223Arg多态性位点AA型患者对二甲双胍敏感,降糖疗效较好。

Objective To evaluate the relationship between the leptin receptor gene Gln223Arg polymorphism and Type 2 diabetes(T2DM)combined with hyperuricemia(HUA)patients and the therapeutic effect of metformin.Methods 160 patients with T2DM admitted to our hospital from March,2018 to December,2019 were divided into the T2DM group(n=80)and combined group(n=80)according to whether T2DM patients were combined with HUA.The distribution frequency of the leptin(LEP)receptor gene Gln223Arg polymorphism was determined by PCR-restriction fragment length polymorphism(PCR-RELP)method,and the multivariate unconditional logistic regression was applied to analyze the risk factors of patients with T2DM combined with HUA.At the same time,T2DM combined HUA patients were treated with metformin,and the relationship between the efficacy of metformin and each genotype was analyzed.Results There were no significant differences in gender,age,total cholesterol(TC),and high-density lipoprotein(HDL-C)between the two groups(P>0.05).Smoking history,coronary heart disease history,course of diabetes,body mass index(BMI),triglycerides(TG),low density lipoprotein(LDL-C),glycosylated hemoglobin(HbA1c),insulin resistance index(HOMA-IR),uric acid(UA),and LEP in the combined group were all higher than those in the T2DM group(P<0.05).For both groups,when we compared the expected and observed values of each genotype of the leptin receptor Gln223Arg,there was no difference(all P>0.05),which conformed with the Hardy-Weinberg equilibrium law.Compared with the T2DM group,the combined group’s Gln223Arg locus type AA and AG significantly decreased(P<0.05),and GG type was significantly increased(P<0.05).Multivariate logistic regression analysis showed that genotype GG,smoking history,coronary heart disease history,diabetes course,BMI,TG,LDL-C,HbA1c,HOMA-IR,uric acid,and LEP were risk factors in patients with T2DM and HUA GG type.The reduction rates of AG type FPG,2hPBG and HbA1 were lower than those of AA type(P<0.05),while the reduction range of GG type FPG,2hPBG and HbA1 was lower than that of AG type(P<0.05).Conclusion T2DM patients with GG genotype may be a susceptibility factor for HUA,and patients with leptin receptor gene Gln223Arg polymorphism site AA type are sensitive to metformin and have a better hypoglycemic effect.