FOXC2基因多态性和2型糖尿病胰岛素抵抗的关系

Relationship between FOXC2 gene polymorphism and insulin resistance in type 2 diabetes mellitus

目的探究叉头框C2(FOXC2)基因与5'端非翻译区(5'-UTR)C512T及G350T多态性和2型糖尿病胰岛素抵抗的关系,为2型糖尿病的发病机制研究提供参考。方法以2014年2月至2017年11月2型糖尿病患者218例作为研究组,同期体检健康者173例作为对照组,采用聚合酶链反应-限制性片段长度多态性分析(PCRRFLP)技术,分析FOXC2 C512T多态性和G350T多态性与2型糖尿病及胰岛素抵抗的相关性。结果与对照组相比,研究组血尿酸(UA)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平和空腹血糖(FPG)、胰岛素抵抗指数(HOMA-IR)显著升高,而总胆固醇(TC)、载脂蛋白A1(Apo A1)、空腹胰岛素(FINS)水平显著降低,差异均有统计学意义(P <0. 05,P <0. 01)。两组FOXC2基因的突变位点C512T检测CC、CT、TT 3种基因型,G350T位点检测到GG、GT、TT 3种基因型,基因型频率分布符合Hardy-Weinberg平衡,且各基因型及等位基因频率在研究组和对照组间总体分布差异无统计学意义(P> 0. 05)。Logistic回归分析显示,C512T和G350T基因型分布频率及等位基因频率与2型糖尿病发生风险均无相关性(P> 0. 05)。2型糖尿病患者C512T CC、CT、TT这3种基因型体质指数(BMI)、TG、FINS、HOMA-IR比较均有统计学差异(P <0. 05,P <0. 01);G350T GG、GT、TT这3种基因型BMI、TG、高密度脂蛋白胆固醇(HDL-C)水平比较均有统计学差异(P <0. 01)。结论 2型糖尿病患者FOXC2基因5'-UTR C512T多态性与胰岛素抵抗和脂质代谢有关,G350T多态性与胰岛素抵抗无关而仅与脂质代谢有关,但两者均与糖尿病发生风险无明显相关性。

Objective To investigate the association of the polymorphism of C512 T and G350 T at 5＇ untranslated region（UTR） of forkhead box C2（FOXC2） genewith insulin resistance in type 2 diabetes to provide reference for the study of pathogenesis of type 2 diabetes. Methods A total of 218 patients with type 2 diabetes between February 2014 and November 2017 were selected as study group,and 173 healthy subjects at the same time from medical examination were selected as control group. Polymerase chain reaction-restrictive fragment length polymorphism（PCR-RFLP） was used to analyze the correlation of polymorphisms of FOXC2 C512 T and G350 T with type 2 diabetes and insulin resistance. Results Levels of blood uric acid（UA）,triglycerides（TG）,low density lipoprotein cholesterol（LDL-C） and fasting blood glucose（FPG）and insulin resistance index[（Homeostasis model assessment（HOMA）-IR]in study group were significantly higher than those in control group,and total cholesterol（TC）,apolipoprotein A1（Apo A1）,fasting insulin（FINS） in study group were significantly lower than those in control group（P〈0. 05,P〈0. 01）. In study group and control group,the CC,CT and TT genotypes were found at C512 T mutation site of FOXC2 gene,and the GG,GT and TT genotypes were found at G350 T mutation site of FOXC2 gene. All of the genotype frequency distributions were in accord with the Hardy-Weinberg equilibrium test,and there was no significant difference in the overall distribution of genotypes and allele frequency between study group and control group（P〉0. 05）. Logistic regression analysis showed that there were no significant correlations of the frequencies of genotype distribution and allele frequency at C512 T site and G350 T site with the risk of the occurrence of type 2 diabetes（P〉0. 05）. In patients with type 2 diabetes,there were significant differences in body mass index（BMI）,TG,FINS,HOMA-IR for CC,CT,TT genotypes of C512 T site（P〈0. 05,P〈0. 01）,and there were significant differences in BMI,TG and high density lipoprotein cholesterol（HDL-C） levels for CC,CT,TT genotypes of G350 T site（all P〈0. 01）.Conclusions In patients with type 2 diabetes,thepolymorphism of C512 T at FOXC2 gene 5＇-UTR is related to insulin resistance and lipid metabolism,while the polymorphism of G350 Tat FOXC2 gene 5＇-UTR is not related to insulin resistance and is related to lipid metabolism only. However,neither of them has significant association with the risk of onsetofdiabetes.