摘要
目的探讨中国北方人群肾病蛋白（Nephrin）基因G349A多态性对IgA肾病蛋白尿程度，肾功能以及预后的影响。方法选择经肾活检病理诊断确诊的原发性IgA肾病患者532例，采用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）方法检测NPHSI基因G349A多态性，选取单纯血尿和大量蛋白尿的IgA患者各16例进行PCR产物测序，对酶切结果进行验证。收集患者的年龄、性别、尿蛋白程度、肾功能和病理等临床资料，比较不同基因型之间临床表现的差异。并且对其中138例患者进行了随访观察，研究IgA肾病患者不同基因型对预后的影响。结果在具有完整临床资料的532例IgA肾病患者中，单纯性血尿与蛋白尿，以及不同程度蛋白尿患者中，各等位基因及基因型的分布无统计学意义，然而，肾活检时肾功能损害重的患者[估计肾小球滤过率，eGFR〈60ml·min^-1·（1.73m^2）^-1]携带G等位基因的基因型（AG／GG）的频率明显高于eGFR≥60ml·min^-1·（1．73m^2）^-1的患者，有统计学差异（P=0．008）；多因素Logistic回归分析提示NPHS1的G349A基因型AG／GG是除发病时年龄、高血压、蛋白尿外引起肾脏损害加重的独立危险因素（P=0．011，OR=2．041），采用Cox比例风险模型将多因素对预后的影响进行分析，结果提示G349A基因型GG是除发病时年龄、高血压、蛋白尿和发病时eGFR水平以外影响肾病患者预后的独立危险因素（P〈0．001，OR=14．086）。结论本研究提示NPHS1基因G349A多态性的G等位基因及AG／GG基因型与IgA肾病患者发病时。肾脏损害的严重程度相关，GG基因型和IgA肾病患者的预后相关。
Objective To investigate the association of the polymorphism of NPHS1, coding gene of nephrin, with the degree of proteinuria, renal function, and prognosis of IgA nephropathy （IgAN） in patients in north China. Methods Peripheral blood samples were collected from 532 patients with IgAN confirmed by biopsy, 285 males and 230 females, aged （31 ± 11 ）. Genomic DNA was isolated from the peripheral blood leucocytes. Polymorphism of the exon G349A of NPHS1 was detected by polymerase chain reaction combined with restriction fragment length polymorphism （PCR-RFLP）. 138 patients were followed up for 4 - 99 months. The correlation between the NPHS1 polymorphism and renal function at the time of renal biopsy, and that between NPHS1 polymorphism and the prognosis were analyzed. Results The frequency of the genotype with the allele G （AG/GG） rate （eGFR） 〈60ml·min^-1·（1.73m^2）^-1 was in the patients with the estimated glomerular filtration significantly higher than that of the patients with the eGFR 〉 60ml·min^-1·（1.73m^2）^-1（ P = 0. 008 ）. Even after adjusting for the effects of proteinuria , hypertension, and age, AG/GG genotype was an independent risk factor of the exacerbation of renal damage at the time of diagnosis（ P = 0.011 ）, and GG genotype was an independent risk factor of the prognosis （ P 〈 0. 001 ）. Conclusion G allele and AG/GG genotype are associated with the severity of renal function at the time of diagnosis the GG genotype is associated with the prognosis of IgAN patients.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2009年第13期881-885,共5页
National Medical Journal of China
基金
国家自然科学基金（30670981）
2008年度国家杰出青年科学基金（30825021）
卫生部公益基金（200802052）
