2型糖尿病肾病患者血管生成素2A1087G基因多态性的研究  

Relationship between Angiopoietin-2 A1087G Polymorphism and Type 2 Diabetic Nephropathy

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,云南省昆明市650032 [2]云南省第一人民医院遗传诊断中心 [3]昆明医科大学第二附属医院内分泌科

出　　处：《中国全科医学》2013年第11期1216-1220,共5页Chinese General Practice

摘　　要：目的探讨血管生成素2(Ang-2)A1087G基因多态性与2型糖尿病(T2DM)肾病的相关性。方法选取2010年1月—2012年1月云南省第一人民医院、昆明医科大学第二附属医院内分泌科收治的T2DM患者1 021例(T2DM组)及体检健康者254例(NC组)。然后根据尿清蛋白排泄率(UAER)将T2DM组患者分为3组:T2DM无糖尿病肾病(DN)组(DN0组,431例)、T2DM合并微量蛋白尿组(DN1组,322例)、T2DM合并大量蛋白尿组(DN2组,268例)。收集各组受检者的临床及生化指标,检测各组Ang-2 A1087G基因外显子4的Ang-2多态基因型。结果 (1)各组受检者Ang-2 A1087G的基因型频率和等位基因频率比较,差异均有统计学意义(P<0.05);其中DN0组、DN1组、DN2组患者Ang-2 A1087G AG+GG基因型频率(39.0%、41.9%和44.8%)和G等位基因频率(37.8%、30.3%和33.6%)高于NC组(24.4%和19.1%),差异均有统计学差异(P<0.05)。(2)各组受检者血压、糖化血红蛋白(HbA1c)、肾小球滤过率(eGFR)、空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛β细胞功能指数(HOMA-IS)、胰岛素抵抗指数(HOMA-IR)、单核细胞趋化蛋白1(MCP-1)、Ang-2水平比较,差异均有统计学意义(P<0.05)。(3)多元Logistic回归分析显示:Ang-2 A1087G的AG+GG基因型、G等位基因、血清Ang-2水平、收缩压、HbA1c、FBG、MCP-1、HOMA-IS、eGFR与DN有回归关系(P<0.05)。校正年龄、性别、糖尿病病程、HbA1c、血压等因素影响后,AG+GG基因型相对AA基因型发生DN0(即T2DM无DN)的危险性增加1.823倍〔95%CI(1.557,4.221),P=0.011〕,G等位基因发生DN0的风险是A等位基因的1.442倍〔r=1.321,OR=1.442,95%CI(2.320,4.178),P=0.030〕;发生DN1(即T2DM合并微量蛋白尿)的危险性增加1.778倍〔95%CI(2.356,5.220),P=0.010〕,G等位基因发生DN1的风险是A等位基因的1.984倍〔r=1.021,OR=1.984,95%CI(2.621,4.574),P=0.027〕;发生DN2(即T2DM合并大量蛋白尿)的危险性增加1.991倍〔95%CI(3.560,6.229),P=0.001〕,G等位基因发生DN2的风险是A等位基因的1.881Objective To investigate the correlation between angiopoietin -2 （Ang -2 ） A1087G polymorphism and type 2 diabetic nephropathy （DN）. Methods （ 1 ） A total of 1 021 patients with type 2 diabetes mellitus （ T2DM group） and 254 healthy people （NC group） visiting the First People＇s Hospital of Yunnan Province and the Second Affiliated Hospital of Kunming Medical University between January 2010 and January 2012 were selected. According to urinary albumin excretion rate （UAER）, the T2DM group was divided into three subgroups： T2DM without DN group （DN0 group, 431 cases）, T2DM with microalbuminuria group （DN1 Group, 322 cases）, and T2DM with massive proteinuria group （DN2 group, 268 cases）. Clin- ical and biochemical indicators of subjects in each group were collected. The exon 4 of Ang -2 A1087G was tested for polymorphism. Results （ 1 ） Ang - 2 A1087G gene frequency and allele frequency of subjects in each group were significantly different （P 〈0. 05）. The DN0, DN1, and DN2 group＇s AG ＋ GG frequency （39. 0% , 41.9% and 44. 8% ） and the G allele frequency （37.8%, 30. 3% and 33.6% ） were significantly higher than those of the NC group （24. 4% and 19. 1%, P 〈0. 05）. （2） Significant differences were observed among the groups in blood pressure, glycosylated hemoglobin （I-IbAlc）, glomerular filtration rate （eGFR）, fasting blood glucose （FBG）, fasting insulin （FINS）, 13-cell function index （HOMA-IS）, insulin resistance index （HOMA -IR）, monocyte chemoattractant protein - I （MCP - 1）, and Ang -2 level （P 〈0. 05）. （3） Multiple Logistic regression analysis showed that Ang - 2 AlO87G AG ＋ GG genotype, G allele, serum Ang - 2 level, systolic blood pressure, HbA1c, FBG, MCP-1, HOMA-IS, and eGFR had correlation with DN （P〈0.05）. After adjusting for age, sex, disease course, HbA1c, blood pressure, and other factors, AG ＋ GG genotype had 2. 823 times the risk of developingDNO [95%CI （1.557, 4. 221）, P=0.011], 2.

关 键 词：血管生成素2 多态性 单核苷酸 糖尿病 2型 糖尿病肾病 

分 类 号：R587.24[医药卫生—内分泌]