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

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.

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.

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/TT 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).

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.