[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
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.
No preview · Article · Jul 2006 · Zhonghua nei ke za zhi [Chinese journal of internal medicine]
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Jun 2006 · Zhonghua yi xue za zhi