甘露糖结合凝集素基因多态性与IgA肾病临床表现及其预后相关  

Correlation between mannose binding lectin gene polymorphisms and clinical manifestation and outcome of patients with IgA nephropathy

作　　者：戚超君[1] 施蓓莉[1] 牟姗[1] 王琴[1] 张敏芳[1] 顾乐怡[1] 戴慧莉[1] 倪兆慧[1] 

机构地区：[1]上海交通大学医学院附属仁济医院肾脏内科,分子细胞肾病实验室,上海200127

出　　处：《上海医学》2014年第5期398-402,共5页Shanghai Medical Journal

基　　金：973课题(2012CB517602);十二五国家科技支撑计划(2011BAI10B04);国家自然科学基金(81370794;81373865);上海市高级中西医结合人才培养项目(ZYSNXD012-RC-ZXY017)资助

摘　　要：目的研究IgA肾病患者甘露糖结合凝集素(MBL)基因多态性对患者血清MBL水平,以及临床、病理表现和预后的影响。方法入选93例IgA肾病患者,留取患者血清和全血DNA标本,检测患者MBL基因单核苷酸多态性(SNP)和血清MBL表达水平。结果 IgA肾病患者MBL基因启动子-221位点和外显子1区54号密码子位点存在SNP现象。与外显子区野生型GGC/GGC型患者比较,外显子区54号密码子位点突变(G→A,包括外显子区杂合子GGC/GAC型和纯合子GAC/GAC型)患者舒张压、血清肌酐、血清IgG、肾小球球性/节段性硬化比例(GGS)和肾小管间质-损伤(TID)指数均显著升高(P值均<0.05),而血清IgA显著降低(P<0.05)。外显子区杂合子GGC/GAC型和外显子区纯合子GAC/GAC型患者肾组织合并IgG、IgM沉积阳性率均显著高于外显子区野生型GGC/GGC型患者(P值均<0.05)。Cox回归分析显示,G→A(β=2.460,P=0.033)、血清肌酐(β=0.966,P=0.04)、舒张压(β=1.272,P=0.045)、TID指数(β=0.202,P=0.048)是预测IgA肾病患者肾脏预后的独立危险因素,而启动子区-221位点基因多态性与IgA肾病患者的临床、病理和肾脏预后无关联。结论 MBL基因54号密码子位点变异IgA肾病患者血清MBL水平显著下降,其临床、病理表现较重,肾脏预后较差,MBL基因多态性可能是IgA肾病患者预后不良的危险因素之一。Objective To investigate the single nucleotide polymorphism （SNP） of mannose binding lectin （MBL） gene and serum MBL level in patients with IgA nephropathy （IgAN） and their relationship with patients＇ clinical, pathological manifestations and outcomes. Methods A total of 93 IgAN patients were recruited in this study. DNA samples from patients＇ serum and whole blood were collected. MBL polymorphism and serum MBL level were detected and analyzed. Results SNP was found in promoter -221 （G→C） and exon 1 ＋ 54 （G→A） in IgAN patients. Compared with those of wild type （GGC/GGC）, patients with variant allele （GAC） in exon 1 region had elevated baseline diastolic blood pressure, serum creatinine level, serum IgG level, percentage of glomerular/segmental sclerosis （GGS） and tubular-interstitial damage （TID, all P 〈 0. 05）, and decreased baseline serum IgA level （P〈0.05）. Higher percentage of glomerular deposition of IgG and IgM were found in patients with gene variant （both P 〈 0. 05）. Cox regression analysis showed that exon 1 （＋ 54） gene polymorphism （β = 2. 460, P = 0. 033）, baseline serum creatinine （β = 0. 966, P = 0. 04）, diastolic blood pressure （β = 1. 272, P = 0. 045） and TID （β = 0. 202, P = 0. 048） were independent risk factors of prognosis in IgAN patients, while promoter -221 gene polymorphism was not significantly related to clinical and pathological manifestations and prognosis. Conclusion Patients with MBL gene variation （exon 1） have a low serum MBL level, severe clinical and histological manifestations, and poor renal outcome. MBL gene SNP may be one of the risk factors of poor prognosis in patients with IgAN.

关 键 词：IGA肾病 甘露糖结合凝集素 单核苷酸多态性 预后 

分 类 号：R692.3[医药卫生—泌尿科学]