2型糖尿病肾病患者外周血E-选择素表达水平及其基因G98T和A561C位点多态性与代谢指标的相关性研究

Association of E-selectin and Its Gene G98T and A561C Polymorphisms with Type 2 Diabetic Nephropathy

目的 探讨2型糖尿病肾病(type 2 diabetic nephropathy)患者外周E-选择素(E-selectin)表达水平及其基因G98T和A561C位点多态性与代谢指标相关性。方法 选取陕西省人民医院2020年9月~2021年10月确诊的2型糖尿病肾病患者203例作为糖尿病肾病组。依据糖尿病肾病分期分为5组:AⅠ组39例,AⅡ组42例,AⅢ组40例,AⅣ组47例,AⅤ组35例,以同期40例健康体检者为对照组。采用酶联免疫吸附法(ELISA法)测定血清可溶性E-选择素水平,聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测E-选择素G98T和A561C基因的基因型和等位基因,Pearson相关性分析E-选择素及基因多态性与2型糖尿病肾病代谢指标的关系,多因素logisitic回归分析影响2型糖尿病肾病严重性指标。结果 糖尿病肾病组E-选择素水平(42.34±12.35μg/L)高于对照组(8.10±3.60μg/L),差异有统计学意义(t=7.43,P<0.05),且AⅠ~AⅤ组E-选择素水平随糖尿病肾病疾病严重程度增加而升高,差异有统计学意义(F=4.57,P<0.05)。糖尿病肾病组E-选择素基因G98T位点T等位基因(20.70%),A561C位点C等位基因(14.30%)频率明显高于对照组(7.50%,6.25%),差异均有统计学意义(χ^(2)=8.23,6.44,均P<0.05)。Pearson相关性分析结果显示E-选择素水平、E-选择素G98T位点TT基因型,A561C位点CC基因型与代谢指标(BUN,Cr,TG,TC,FPG,HbAlc,FINS,HOMA-IR)呈正相关(r=0.21~0.73,均P<0.05)。多因素Logisitic回归分析结果显示BUN,Cr,TG,TC,FPG,HbAlc,FINS,HOMA-IR,E-选择素水平及E-选择素G98T位点TT基因型,A561C位点CC基因型均为2型糖尿病肾病的独立危险因素(OR=1.13~1.94,均P<0.05)。结论 E-选择素及其基因G98T位点和A561C位点多态性与代谢指标密切相关,是2型糖尿病肾病的独立危险因素,可为2型糖尿病肾病诊疗提供一定参考价值。

Objective To investigate the correlation between the expression level of E-selectin in peripheral blood of patients with type 2 diabetic nephropathy and the polymorphism of G98T and A561C loci of their genes and metabolic indexes.Methods A total of 203 patients with type 2 diabetic nephropathy diagnosed in Shaanxi Provincial People’s Hospital from September 2020to October 2021 were selected as diabetic nephropathy group,according to the stage of diabetic nephropathy.They were divided into 5 groups:AⅠgroup(39 cases),AⅡgroup(42 cases),AⅢgroup(40 cases),AⅣgroup(47 cases),AⅤgroup(35cases),and 40 healthy subjects were selected as control group.The serum soluble E-selectin level was determined by enzymelinked immunosorbent assay(ELISA).The genotypes and alleles of E-selectin G98T and A561C genes were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Pearson correlation analysis was used to analyze the relationship between E-selectin and gene polymorphism and metabolic indexes of type 2 diabetic nephropathy.Multivariate logisitic regression analysis was used to analyze the severity indexes of type 2 diabetic nephropathy.Results The level of E-selectin in diabetic nephropathy group(42.34±12.35μg/L)was higher than that in control group(8.10±3.60μg/L),and the difference was statistically significant(t=7.43,P<0.05).The level of E-selectin in AⅠ~AⅤgroup increased with the severity of diabetic nephropathy,and the difference was statistically significant(F=4.57,P<0.05).The frequencies of T(20.70%)allele at G98T and C(14.30%)allele at A561C in diabetic nephropathy group were significantly higher than those in control group(7.50%,6.25%),the differences were statistically significant(χ^(2)=8.23,6.44,all P<0.05).Pearson correlation analysis showed that E-selectin level,TT genotype at E-selectin G98T site and CC genotype at A561C site were positively correlated with metabolic indexes(BUN,Cr,TG,TC,FPG,HbAlc,FINS,HOMA-IR)(r=0.21~0.73,all P<0.05).Multivariate Logistic regression analysis showed that BUN,Cr,TG,TC,FPG,HbAlc,FINS,HOMA-IR and E-selectin levels,TT genotype at E-selectin G98T site and CC genotype at A561C site were independent risk factors for type 2 diabetic nephropathy(OR=1.13~1.94,all P<0.05).Conclusion E-selectin and its gene G98T,A561C polymorphism were closely related to metabolic indexes,and would be independent risk factors for type 2 diabetic nephropathy,which can provide certain reference value for the diagnosis and treatment of type 2 diabetic nephropathy.