[Association of single nucleotide polymorphism of megsin gene with IgA nephropathy]

To investigate whether the single nucleotide polymorphisms (SNPs) in the gene of megsin, a novel serine protease inhibitor, account for the pathogenicity of IgA nephropathy (IgAN).

A comprehensive megsin gene survey, including the entire coding region, part of the regulatory region, and exon-intron connection region, was performed by PCR-direct sequencing on the DNA samples of peripheral blood from 12 randomly selected IgAN patients and 12 randomly selected healthy persons. Eight SNPs with moderate or high frequencies (with the frequency > 5%) selected from the 11 SNPs found were used as candidate SNPs. Then 210 IgAN patients proven by renal-biopsy, all of Chinese Han nationality, and 103 normal volunteers were recruited. The 8 candidate SNPs were genotyped by direct sequencing or PCR-RFLP and a case-control association study was carried out.

The SNP of 267G/A in 5'untranslated region within exon1 was significantly associated with IgAN. The frequency of AG/AA genotype of the IgA patients was 29.0%, significantly higher than that of the controls (16.5%, P < 0.05). The frequency of A allele of the IgA patients was 14.8%, significantly higher than that of the controls (8.7%, P < 0.05). The odds ratio of AG/AA genotype versus GG genotype was 2.07 with the 95% confidence interval of 1.15 - 3.74. The linkage disequilibrium between two SNPs existed commonly within one gene.

267G/A in megsin gene is associated with IgAN susceptibility. AG and AA genotypes are the risk factors of pathogenesis of IgAN.