Angiopoietin-2基因多态性与2型糖尿病及糖尿病慢性肾脏疾病的相关性研究  

Correlation of angiopoietin-2 gene polymorphism with type 2 diabetes mellitus and chronic kidney disease in diabetes

作　　者：何泉[1] 罗海明[1] 朱宝生[2] 唐新华[2] 蒋绿芝[3] 

机构地区：[1]云南省第一人民医院急诊科,昆明650031 [2]云南省第一人民医院遗传诊断中心,昆明650031 [3]昆明医科大学第二附属医院内分泌科

出　　处：《中国糖尿病杂志》2013年第4期315-321,共7页Chinese Journal of Diabetes

摘　　要：目的研究血管生成素-2(Angiopoietin-2,Ang-2)基因多态性与T2DM及CKD的相关性。方法纳入525例T2DM患者(T2DM组)和255名健康人群(NC组),应用限制性片段长度多态性(RFLP-PCR)对Ang-2 759T→G→C及Ang-2 1087A→G进行基因检测;同时应用等位基因特异性聚合酶链式反应(ARMS-PCR)对Ang-2 1233A→G进行基因检测。根据UAER将T2DM组分为3个亚组:未合并CKD组(CKD0组)、合并微量蛋白尿组(CKD1组)和合并大量蛋白尿组(CKD2组),比较基因型、等位基因频率分布及临床变量间的差异。结果 Ang-2 1087A→G(AG+GG)、Ang-2 1233A→G(AG+GG)基因型频率和1087G、1233G等位基因频率在T2DM与NC组间比较,差异有统计学意义,在CKD0、CKD1、CKD2组间比较差异有统计学意义。多元回归分析显示,Ang-2 1078G、Ang-2 1233G等位基因、SBP、FPG、HbA1c、肾小球滤过率(eGFR)、单核细胞趋化蛋白(MCP-1)、Ang-2血清学水平、HOMA-β是糖尿病慢性肾脏疾病(CKD)的危险因素。Ang-2 1078G、Ang-2 1233G等位基因、MCP-1、Ang-2血清学水平与IR呈正相关。结论 Ang-2 1087G、Ang-2 1233G等位基因变异可能与CKD相关,同时Ang-21087A→G、Ang-2 1233A→G与T2DM相关。而Ang-2 759T→G→C与T2DM及CKD无相关性。Ang-2 1087G、Ang-2 1233G等位基因、SBP、FPG、HbA1c、HOMA-β是发生CKD的危险因素。Objective To evaluate the correlation of angiopoietin-2 gene polymorphism with type 2 diabetes mellitus and chronic kidney disease in diabetes. Methods The 525 T2DM patients and 255 healthy subjects （NC） were enrolled. According to their UAER, the T2DM patients were subdivided into non-CKD group （CKD0）, microalbuminuria group （CKEh）, and macroalbuminuria group （CKDz）. PCR- RFLP was employed to detect genotypes of the angiopoietin-2 gene polymorphrism in 2 759 （exon-2） and 1087 （exon-4） ; while the angiopoietin-2 gene polymorphrism in 1233 （exon-5） was detected. Meanwhile the fasting levels of glucose, insulin, TG, TC, HbAlc, blood presure, BMI, eGFR and MCP-1, angiopoietin-2 levels （plasma） were examined. Results The frequency of angiopoietin-2 1087 （AG＋ GG） and angiopoietin-2 1233 （AG＋GG） genotypes and the frequency of 1087G and 1233G allele in T2DM group were statistically different from those of normal controls. The between-group differences among CKD0, CKDt and CKD2 groups were statistically significant. The multivariate logistic regression analysis showed that the angiopoietin-2 1078G and angiopoietin-2 1233G alleles, BMI, FPG, HbAlc, HOMA-β, systolic blood pressure, MCP-1, and eGFR were the risk factors for type 2 CKD. The angiopoietin-2 1078G and angiopoietin-2 1233G alleles, and the levels of serum MCP-1 and Ang-2 were positively relatedwith insulin resistance. Conclusion The allele variation of angiopoietin-2 1078G and angopoietin-2 1233G may be associated with CKD. At the same time, the allele mutation of angiopoietin-2 1087G and angiopoietin-2 1233G is probably related with T2DM. Whilst the angiopoietin-2 759T→G→C gene is not associated with T2DM and CKD. The angiopoietin-2 1078G and angiopoietin-2 1233G alleles, BMI, systolic blood pressure, FPG, HbA1c, and HOMA-β are the risk factors for CKD.

关 键 词：血管生成素-2 基因 多态性 糖尿病 2型 糖尿病慢性肾脏疾病 

分 类 号：R692[医药卫生—泌尿科学]