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甘露糖结合凝集素基因多态性与IgA肾病临床表现及预后相关
Association between Mannose binding lectin gene polymorphisms and clinical manifestation, outcome of patients with IgA nephropathy
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DOI:
作者:
戚超君
Qi Chaojun, Shi Beili, Mou shan, Wang qin, Zhang Minfang, Gu leyi, Dai Huili, Ni zhaohui
作者单位:
上海交通大学医学院附属仁济医院
Department of Nephrology, Molecular Cell Lab for Kidney Disease, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University
关键词:
IgA肾病;甘露糖结合凝集素;单核苷酸多态性;预后
IgA nephropathy; Mannose binding lectin; Single nucleotide polymorphism; Prognosis
摘要:
目的:研究IgA肾病(IgAN)患者甘露糖结合凝集素(MBL)基因多态性对患者血清MBL浓度,临床,病理表现及预后的影响。方法:入选93例IgAN患者,留取患者血清及全血DNA标本,检测患者MBL基因单核苷酸多态性(SNP)及血清MBL表达水平,分析MBL基因SNP与IgAN患者血清MBL水平,临床,病理表现及预后的关系。结果:IgAN患者MBL基因启动子-221位点和外显子1区54位点存在SNP现象。MBL基因54位点变异IgAN患者血清MBL水平显著降低(P<0.001),初始舒张压、血肌酐、肾小球球性/节段性硬化比例(GGS)及肾小管间质-损伤指数(TID)显著较高,肾脏预后显著较差(P=0.005)。Cox回归分析发现,54位点A等位基因(β=2.460,P=0.033)、初始血肌酐(β=0.966,P=0.04)、TID(β=0.202,P=0.048)是预测IgAN患者肾脏预后的独立危险因素。而启动子区域-221位点基因多态性与IgAN患者的临床、病理及肾脏预后无显著关联。结论:MBL基因54位点变异IgAN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IgAN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 manifestation and outcome. Methods 93 patients with IgAN were recruited in this study. Integrated capillaryelectrophoresis was used to detect MBL polymorphism in peripheral blood DNA of IgAN patients. ELISA was used to detect patients’ serum MBL level. Results were taken together to analysis MBL polymorphism and its correlation with serum MBL level, clinical, pathological manifestation and renal outcome. Results We found SNP in promoter -221 (G→C) and exon 1 +54 (G→A) in our IgAN patients. The variant allele (GAC) in exon 1 region was markedly associated with lower serum MBL levels (P<0.001). Compared with wild-type, patients with gene variant had elevated baseline serum creatinine levels (P=0.048), higher percentage of glomerular/segmental sclerosis (P=0.024), higher tubular-interstitial damage (P=0.049) and worse renal outcome (P<0.001). Cox analysis further showed that exon 1 (+54) gene polymorphism (β=2.460,P=0.033), baseline serum creatinine levels (β=0.966,P=0.04) and TID (β=0.202,P=0.048) were independent factors of renal prognosis in IgAN patients. Conclusion Patients with MBL gene variation had a lower serum MBL level and much more severe clinical and histological manifestation. And MBL gene variation was also correlated with poor renal outcome. MBL gene SNP might be one of the factors of renal prognosis in patients with IgAN .
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