Objective: IgA nephropathy is one of the most common form of primary glomerulonephritis throughout the world and a main renal disease which causes renal failure. P-selectin plays an important role in the pathogenesis and development of IgA nephropathy. The purpose of this study is to find a possible relationship between P-selectin gene polymorphism and IgA nephropathy.
Methods: In this study, a comprehensive P-selectin gene survey, including entire coding region, part of regulatory region and exon-intron connection region, was performed with PCR-direct sequencing and 16 single nucleotide polymorphism (SNPs) were detected. Then 210 renal-biopsy proven sporadic IgA nephropathy cases of Chinese Han nationality and 103 normal volunteers were recruited. 9 candidate SNPs (frequency > 5%) in P-selectin gene of both the case and control groups were genotyped with direct sequencing and a case-control association study was carried out.
Results: It was revealed that the SNP of -825A/G in promoter region of P-selectin gene was significantly associated with IgA nephropathy. Both the frequency of AG/GG genotype (21.9% vs 34.9%, P < 0.05) and G allele (11.4% vs 18.4%, P < 0.05) were less in the IgA nephropathy cases than in the healthy controls. Those carrying the low frequency G allele (AG/GG genotype) had a protective effect on the morbidity of IgA nephropathy and the odds ratio for the IgA nephropathy patients versus controls was 0.522 with AG/GG genotype versus AA genotype. Within the IgA nephropathy group, patients with AA genotype tended to present higher level of serum creatinine and soluble P-selectin than those carrying at least one G allele (AG/GG genotype) (P < 0.05).
Conclusion: The SNP of -825A/G in the promoter region of P-selectin gene was significantly associated with IgA nephropathy susceptibility and patient's renal function, thus suggesting the genetic effect of P-selectin gene in the pathogenesis of IgA nephropathy.