内蒙古汉族IgA-N患者TNF-α基因多态性与临床特征、病理类型及预后关系的研究

To Study the Relationship Between the Gene Polymorphism of TNF-αand Clinical Character,Pathological Types,Prognosis in Patients with IgA Nephropathy of Han Nationality Chinese in the Inner Mongolia Autonomous Region

目的:在内蒙古开展汉族IgA肾病(IgA-N)患者TNF-α基因多态性与临床特征、病理类型及预后关系的研究。方法:选100例内蒙古汉族IgA-N患者(对其中33例患者进行1月～60月的随访)及105例正常对照组,采用聚合酶链式反应-限制性片段长度多态性分析(PCR-RFLP)技术检测TNF-α基因多态性和等位基因频率,分析不同基因型与IgA-N临床特征、病理类型及预后的关系。结果:①IgA-N患者TNF-α的三种基因型与健康对照组间差异无显著性(P>0.05)。②TNF-α的三种基因型与IgA-N患者的年龄、血压、血尿、尿蛋白、白蛋白、肾功能及病理间无显著关系。③多因素logistic回归分析表明,高血压病史、蛋白尿是除TNF-α基因型、Haas分级及发病时年龄外引起肾脏损害加重的独立危险因素。④采用Cox比例风险模型将多因素对预后的影响进行分析,结果显示,TNF-α不同基因型、发病时CCr水平是除蛋白尿、Haas分级、高血压病史和肉眼血尿以外影响IgA-N患者预后的独立危险因素。⑤TNF-α的Kaplan-Meier生存曲线显示,以肾穿为零点,各种TNF-α基因型的患者在肾穿后肾功能的下降倾向于TNF-α1/2基因型最快,TNF-α1/1基因型次之,TNF-α2/2最慢。结论:①高血压病史、蛋白尿是除TNF-α基因型、Haas分级及发病时年龄外引起肾脏损害加重的独立危险因素;②TNF-α不同基因型、发病时CCr水平是除蛋白尿、Haas分级、高血压病史和肉眼血尿以外影响肾病患者预后的独立危险因素;③TNF-α1/2基因型可能是IgA-N慢性化进展的危险因子之一。

Objective To Study the relationship between the gene polymorphism of TNF-ot and clinical chracter, pathological types, and prognosis in patients IgA nephropathy（IgA-N） of han nationality chinese in the inner mongolia autonomous region. Meth- ods One hundred patients with biopsy were proven IgA-N. Thirty-three patients had been followed-up for 1-60months. One hundred and five healthy donors served as normal controls. The single base change polymorphism in TNF-ct gene were determined by using PCR-RFLP. TNF-ot genetype and allele frequency were compared between patients with IgA-N and normal controls. In addition, associ- ations of TNF-α polymorphism with blood pressure, hematuria, pmteinuria, pathological lesions prognosis of renal function were analyzed in patients with IgA-N. Results ①Distribution of TNF-α polymorphism in patients with IgA-N and normal controls showed no differ- ence. ② TNF-α polymorphism in patients of IgA-N with blood pressure, hematuria, proteinuria, albumin, pathological lesions progno- sis of renal function proclaimed no difference. ③The logistic regression analysis indicated that even after adjusting for the effect of age of patients, Haas grade and the TNF-α genotype, proteinuria and hypertension were independent risk factors for the deteriorated at thetime of diagnosis. ④ Barring proteinuria, hematuria, hypertension, the TNF-α genotype and renal iunction at the time ol diagnos,s were unique risk factors for the development of IgA-N. ⑤ Kaplan-Meier survival curve of TNF-α show：TNF-cd/2 genetype of renal function declining is the fastest, TNF-α1/1 genetype is faster, TNF-α2/2 genetype is slowly. Conclusion ① Barring age of pa- tients, haas grade and the TNF-α genotype, proteinuria and hypertension were independent risk factors for the deteriorated at the time of diagnosis. ② Barring proteinuria, hematuria, hypertension,the TNF-α genotype and renal function at the time of diagnosis were u- nique risk factors for the development of IgA-N. ③ TNF-α1/2 genetype maybe one of the genetic markers for disease progression in IgA-N of han nationality chinese in the Inner Mongolia autonomous region.