ARHGEF11基因R1467H多态性对汉族2型糖尿病患者血糖和血浆胰岛素水平的影响

Effect of ARHGEF11 gene R1467H G/A polymorphism on the level of blood glucose and fasting insulin during general anesthesia in patients with type 2 diabetes mellitus in Han population

目的探讨Rho蛋白鸟苷酸交换因子11(human Rho guanine nucleotide exchange factor 11,ARHGEF 11)基因R1467H多态性的分布及对2型糖尿病患者血糖(BG)和血浆胰岛素(Ins)水平的影响。方法择期全身麻醉下行胃肠手术的2型糖尿病患者149例,男93例,女56例,年龄24~72岁,ASAⅠ或Ⅱ级,采用聚合酶链反应(PCR)和DNA直接测序技术,对受试者ARHGEF11基因R1467H多态性位点进行基因分型,根据基因型将患者分成野生型纯合子(G/G)组、突变型杂合子(G/A)组、突变型纯合子(A/A)组。于麻醉诱导前(T_0)、插管后1 min(T_1)、切皮时(T_2)、切皮后2h(T_3)、拔管时(T_4)、拔管后10min(T_5)抽取静脉血测定BG和血浆Ins水平,并计算胰岛素抵抗指数(HOMA-IR)。结果与G/G组比较,T_2—T_5时G/A组和A/A组BG、Ins和HOMA-IR均明显升高(P<0.05);与G/A组比较,T_1—T_5时A/A组BG、HOMA-IR和T_3—T_4时Ins明显升高(P<0.05);与T_0时比较,T_1—T_5时G/G组和G/A组患者FBG、HOMA-IR明显升高(P<0.05),T_2—T_5时G/A组Ins和A/A组BG、HOMA-IR明显升高(P<0.05)。结论ARHGEF11基因R1467H多态性是引起汉族2型糖尿病患者血糖和血浆胰岛素水平个体差异及胰岛素抵抗的遗传因素之一。

Objective To investigate the distribution of ARHGEF11 R1467 Hpolymorphism in Han population and to explore the effects of ARHGEF11 gene R1467 Hpolymorphism on the level of blood glucose（BG）and insulin（Ins）during general anesthesia in patients with type 2 diabetes mellitus.Methods A total of 149 patients,93 males and 56 females,aged 24-72 years,ASA physical statusⅠ orⅡ,scheduled for elective gastrointestinal surgery under general anesthesia were recruited into this study.Genotyping of ARHGEF11 gene R1467 H polymorphism was carried out using polymerase chain reaction（PCR）and DNA sequencing methods.The patients were divided into three groups according to their genotypes：group G/G wild homozygote,group G/A mutation heterozygote and group A/A mutation homozygote.BG and Ins were monitored before induction of general anesthesia（T0）,1 min after intubation（T1）,at skin incision（T2）,2 hafter skin incision（T3）,extubation（T4）and 10 min after extubation（T5）,and index of insulin resistance（HOMA-IR）were further calculated.Results Compared with group G/G,BG,Ins and HOMA-IR at T2-T5 were increased significantly in groups G/A and A/A（P 〈 0.05）.Compared with group G/A,the levels of BG,HOMAIR were statistically significant at T1-T5,the level of Ins was obviously higher at T3 and T4 in group A/A（P 〈 0.05）.Compared to T0,the levels of BG,HOMA-IR at T1-T5 were significantly higher in groups G/G and G/A（P 〈 0.05）,the levels of Ins in group G/A and BG,HOMA-IR in group A/A at T2-T5 were still markedly higher than those at T0（P 〈 0.05）.Conclusion The R1467 H G/A polymorphism of ARHGEF11 gene may be involved in the difference of BG and Ins,and it also may contribute to the susceptibility to insulin resistance in Han population under general anesthesia in patients with type 2 diabetes mellitus.