转铁蛋白受体基因多态性与IgA肾病易感性及临床病理表型的相关性

目的:探讨转铁蛋白受体基因(TFRC)多态性与中国汉族人群IgA肾病遗传易感性及临床病理表型的相关性.方法:采用聚合酶链反应-限制片段长度多态性(polymerase chain reaction-restriction fragment length polymor-phism,PCR.RFLP)分析转铁蛋白受体基因TFRC多态性并鉴定基因型,采用病例一对照研究比较正常人与IgA肾病患者基因型的分布频率,并比较不同基因型与患者临床病理表型之间的相关性.结果:1)380例IgA肾病患者TFRC基因的424G/A及-5184C/T多态性与250例正常对照相比,基因型分布频率差异无统计学意义(P>O.05);(2)临床资料显示,年龄、性别、血压、血尿、血肌酐水平、内生肌酐清除率及血清IgA水平等临床指标与TFRC424G/A及一5184C/T基因型不具有相关性.(3)病理资料显示,TFRC基因424G/A和-5184C/T基因型分布与肾活检标本中肾小球系膜区IgA沉积的荧光强度相关,424GG或-5184CC基因型患者系膜区IgA沉积的荧光强度较低,差异有统计学意义(P<0.05),但与肾病理损害程度(Haas分级)无明显相关性.结论:FRC的424G/A及-5184C/T多态性与IgA肾病遗传易感性无关,但与系膜区IgA沉积的荧光强度相关.基因其他部位的多态位点与IgA肾病的发病,以及该基因的多态位点与其他基因的多态位点间的交互作用还需要进一步研究.

Correlation of TFRC polymorphism with the susceptibility and clinicopathologic phenotypes of IgA nephropathy

OBJECTIVE:To explore the association of its polymorphism of TFRC with the susceptibility, clinical and pathologic phenotypes of IgA nephropathy. METHODS: A total of 380 patients with IgA nephropathy and 250 normal controls were enrolled in the study. The regions with 424G/A and -5184C/T polymorphism sites of TFRC were amplified by PCR from genomic DNA and then the PCR-RFLP were performed by restriction enzymes, BanI and BsmA I, respectively. The genetic association of genotypes with the clinical and pathologic phenotypes was analyzed. RESULTS: The distribution of frequency in TFRC was consistent with Hardy-Weinberg equilibrium; however, we found no significant difference in genotypes distribution between patients and controls. There were no differences between genotypes in age, blood pressure, 24 h urine protein excretion, serum creatinine, creatinine clearance and serum IgA. 424G/A and -5184C/T polymorphisms were associated with immunofluorescent intensity of IgA deposit in mesangial area, though there was no difference in pathological lesions evaluated by HAAS grade. CONCLUSION: The polymorphisms of TFRC in 424G/A and -5184C/T sites were not associated with susceptibility to IgA nephropathy, but associated with density of immunofluorescence of IgA in mesangium in our large population based Chinese patients. The association of IgA nephropathy and other polymorphism sites, as well as interaction between TFRC polymorphism and other geneso polymorphisms, neededs to be further investigated.