基质金属蛋白酶-9基因二核苷酸重复序列多态标志ACn多态与2型糖尿病蛋白尿肾病相关  

ACn polymorphism of matrix metalloproteinase-9 gene is associated with proteinuric nephropathy in type 2 diabetes mellitus

作　　者：刘丽梅[1] 郑泰山[1] 李鸣[1] 陆惠娟[1] 李杰[1] 项坤三[1] 

机构地区：[1]上海交通大学附属第六人民医院内分泌代谢科上海市糖尿病研究所,200233

出　　处：《上海医学》2006年第9期628-631,共4页Shanghai Medical Journal

基　　金：国家自然科学基金资助(39900071)

摘　　要：目的探讨基质金属蛋白酶-9(MMP-9)基因二核苷酸重复序列多态标志ACn与中国人2型糖尿病蛋白尿肾病的相关性。方法收集中国人2型糖尿病合并及非合并肾病患者245例,其中非肾病组(Non-DN) 78例,微量蛋白尿肾病组(DN-1)129例。显著蛋白尿肾病组(DN-2)38例；非糖尿病对照组83例。采用荧光染料FAM标记引物5′末端．将聚合酶链反应(PCR)产物进行变性聚丙烯酰胺凝胶电泳,采用基因片段分析法检测个体MMP-9基因ACn的基因型,比较各组间基因型和等位基因频率。结果①共发现9种等位基因,ACn重复数目为16至24。其中以AC21等位基因最为常见,其他等位基因频率大小顺序依次为AC19＞AC20＞AC18。②DN-2组的AC18等位基因频率为11．8%,显著高于Non—DN组的3．8%(P=0．042,OR=3．7．95%CI 1．2～11．4)。③DN-1组的AC20等位基因频率为23．7%,显著低于Non—DN组的13．9%(P=0．016,OR=2．0,95%CI 1．1～3．6)。结论中国人MMP-9基因(AC)n重复数16至24,最常见等位基因为AC21。AC18等位基因可能是糖尿病发生显著蛋白尿肾病的风险因子．而AC20等位基因可能是防止糖尿病微量蛋白尿肾病发生的保护因子。因此,MMP-9基因微卫星多态可能是中国人2型糖尿病肾病的遗传标志。Objective To investigate the association between ACn polymorphism of matrix metalloproteinase-9 （MMP-9） gene and proteinuric nephropathy in Chinese type 2 diabetes mellitus patients. Methods We performed case-control study in 245 Chinese diabetic patients with or without nephropathy and 83 non diabetic controls. Diabetic patients were subdivided into diabetes without nephropathy （Non-DN, n 78）, microalbuminuria nephropathy （DN- 1, n = 129） and macroalbuminuria nephropathy （DN-2, n = 38） groups according to 24h urinary albumin excretion rates （AER）. PCR was performed using primers marked with or without fluorescent dye FAM and Gene Scan was used to detect the genotypes of individual MMP-9 gene repeat series polymorphism marker （AC）n. Finally we compared the frequencies of the genotypes and alleles between various groups respectively. Results We found 9 ACn （n = 16-24） alleles, among them, the allele AC21 was the commonest one. The sequence of frequencies of other alleles from high to low appeared as AC19〉AC2〉AC18. In the DN-2 group, the frequency of allele AC18 was markedly higher than that of DN-0 group （11.8% vs 3.8%）, Fisher＇s two-tailed exact p value was 0. 042 and the odds ratio was 3.7 （95%CI 1.2-11.4）. In comparison with Non-DN group, AC20 allele frequency decreased significantly （23.7% vs 13.9%）, p value was 0. 016 and odds ratio was 2.0（95%CI 1. 1-3.6）respectively. Conclusions MMP-9 gene dinucleotide repeat polymorphism marker （AC）n was found to repeat 9 times, i. e. , n = 16-24 and the AC21 is the commonest one among Chinese patients. The AC18 might be the risk factor of macroalbuninuric nephropathy, whereas AC20 might be the protecting factor from the occurrence of microalbuminuric nephropathy in diabetic patients. Therefore, MMP-9 gene microsatellite polymorphism may be a useful genetic marker of Chinese type 2 diabetic nephropathy. （Shanghai Med J, 2006, 29：628-631）

关 键 词：基质金属蛋白酶-9基因 二核苷酸重复序列多态标志(AC)n 2型糖尿病肾病 微量蛋白尿 显著蛋白尿 

分 类 号：R587.1[医药卫生—内分泌]