·糖尿病分子生物学和遗传学·　　

Angiopoietin-2基因多态性与2型糖尿病及糖尿性病肾脏疾病相关性的研究

　　何泉 罗海明 朱宝生 唐新华 蒋绿芝

　　【摘要】 目的 研究Angiopoietin-2(Ang-2)基因多态性与T2DM及糖尿病性肾脏疾病(DN)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。据尿白蛋白排泄率(UAER)将T2DM组分成3个亚组：未合并DN组(DN0组)，合并微量蛋白尿组(DN1组)和合并大量蛋白尿组(DN2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组与对NC比较差异有统计学意义;DN0、DN1、DN2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、FBG、HbA1c、eGFR、MCP-1、Ang-2血清学水平、HOMA-β是DN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DN相关，同时Ang-2 1087A→G、Ang-2 1233A→G与T2DM相关。而Ang-2 759T→G→C与T2DM及DN无相关性。Ang-2 1087G、Ang-2 1233G等位基因、SBP、FBG、HbA1c、HOMA-β是DN的危险因素。

　　【关键词】 Angiopoietin-2;基因;多态性;糖尿病，2型;糖尿病性肾脏疾病

Correlation of angiopoietin-2 gene polymorphism with type 2 diabetes mellitus and diabetic nephropathy HE Quan, LUO Hai-ming, ZHU Bao-sheng, et al. Department of Emergency, The First People’s Hospital of Yunnan Province, Kunming 650032, China

　　【Abstract】Objective To evaluate the correlation of angiopoietin-2 gene polymorphism with type 2 diabetes mellitus and diabetic nephropathy. Methods The 525 T2DM patients and 255 healthy subjects (NC) were enrolled. According to their albuminuric excretion rate (UAER), the T2DM patients were subdivided into non-DN group (DN0, n=191; UAER<30mg/24h), microalbuminuria group (DN1, n=202; UAER<30mg/24h), and macroalbuminuria group (DN2, n=131; UAER<30mg/24h). PCR-RFLP was employed to detect genotypes of the angiopoietin-2 gene polymorphrism in 759 (exon-2) and 1087 (exon-4); while the angiopoietin-2 gene polymorphrism in 1233 (exon-5) was detected by PCR-AMRS. Meanwhile the fast blood glucose, fast blood insulin, blood pressure, TG, TC, HbA1c, body mass index, 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 allelotypes in the T2DM group were statistically different from those of normal controls in comparison. The between-group differences among DN0, DN1 and DN2 groups were statistically significant. The multivariate Logistic regression analysis showed that the angiopoietin-2 1078G and angiopoietin-2 1233G alleles, BMI, FBG, HbA1c, HOMA-β, systolic blood pressure, MCP-1, and eGFR were the risk factors for type 2 diabetic nephropathy. The angiopoietin-2 1078G and angiopoietin-2 1233G alleles, and the levels of serum MCP-1 and Ang-2 were positively related with insulin resistance. Conclusion The allele variation of angiopoietin-2 1078G and angopoietin-2 1233G may be associated with diabetic nephropathy. 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 diabetic nephropathy. The angiopoietin-2 1078G and angiopoietin-2 1233G alleles, BMI, systolic blood pressure, FBG, HbA1c, and HOMA-β were the risk factors for diabetic nephropathy.

　　【Key words】Angiopoietin-2; Gene; Polymorphism; Diabetes mellitus, type 2; Diabetic nephropathy (DN)