NPHS2基因多态性与中国北方IgA肾病患者的相关性

目的 分析中国北方地区IgA肾病患者NPHS2基因多态性及其与IgA肾病患者蛋白尿和肾功能的关系。方法 将IgA肾病患者按临床表现分为肾病综合征组和单纯血尿组(各16例)。通过基因测序法筛查与中国北方IgA肾病患者蛋白尿水平相关的NPHS2基因的多态性。根据筛查结果,采用PCR-限制性片段长度多态性技术(PCR-RFLP)检测537例原发性IgA肾病患者NPHS2基因的C357T多态性,比较不同基因型之间临床表现的差异。结果 (1)检测到8种基因多态性：-931A＞T、-601C ＞T、19G＞T、171A＞G、357C＞T、IVS3-21C＞T、1023C＞T和1107A ＞G。(2)上述测序结果提示NPHS2基因357T等位基因频率在肾病综合征组明显低于单纯血尿组(0.038比0.125,P＜0.05),说明此多态性可能和IgA患者发生大量蛋白尿相关。故选择C357T多态性做大样本分析。(3)在537例有临床资料的IgA肾病患者中,比较357CC基因型和357CT/TT基因型的患者在性别、肾穿时年龄、血压、肉眼血尿、蛋白尿、发病时肾功能的差别,结果显示携带NPHS2 357CT/TT 基因型的患者24h尿蛋白定量程度较轻(P =0.023)。与肾病综合征组相比,携带T等位基因的患者蛋白尿小于3.5 g/d的比例明显增多(P=0.017)。多因素logistic回归分析表明NPHS2的C357T基因型CT/TT是除高血压病史、发病年龄外,IgA肾病患者发生大量蛋白尿的独立保护因素(P =0.012,OR =0.485,95％ CI0.275 ～0.854)。结论 本研究检测到8种基因多态性,其中NPHS2基因C357T 的T等位基因是中国北方IgA肾病患者发生蛋白尿以及大量蛋白尿的保护因素。

The correlation between NPHS2 polymorphism and IgA nephropathy in northern Chinese patients

Objective To examine the polymorphism in NPHS2 gene of IgA nephropathy in northern Chinese patients and to investigate the possible association of the NPHS2 polymorphism with the development of IgA nephropathy, as well as its clinical and histologic manifestations.Methods The polymorphism of NPHS2 was analyzed by direct DNA sequencing in 32 northern Chinese patients with IgA nephropathy (16 with heavy proteinuria and 16 with isolated hematuria).According to preliminary results, a total of 537 IgA nephropathy patients were genotyped for the NPHS2 C357T polymorphism by PCR combined with restriction fragment length polymorphism (PCR-RFLP). We collected clinical and histologic manifestations for gene analysis in patients with IgA nephropathy, such as age, sex, urine protein excretion and so on.Results Eight NPHS2 polymorphisms (-931A＞T, -601C ＞T, 19G＞T, 171A＞G, 357C ＞ T, IVS3-21C ＞ T, 1023C ＞ T and 1107A ＞ G) were identified.The preliminary results of gene sequencing showed that the frequency of 357T allele in nephrotic syndrome group was obviously lower than isolated hematuria group (0.038 vs 0.125, P ＜0.05).In 537 IgA nephropathy patients with clinical and histologic data, the average urinary protein excretion in the patients with the 357CT/TT genotype was less (P =0.023).The incidence of urinary protein of more than 3.5 g/d was significantly lower in patients with T allele and TT/CT genotype, respectively (P =0.017 and 0.011).The logistic regression analysis indicated that, even after adjusting for the effect of hypertension and age of patients, the CT/II genotype of NPHS2 C357T was an independent protective factor for the urinary protein excretion more than 3.5 g/d(P =0.012,OR = 0.485, 95％ CI 0.275-0.84).Conclusions Eight NPHS2 polymorphisms were identified in northern Chinese IgA nephropathy patients. The frequencies of NPHS2 T allele and TT/CT genotype were the protective factors for urinary protein, especially with that of more than 3.5 g/d.