Mannose-binding protein gene polymorphism influences the patterns of glomerular immune deposition in IgA nephropathy
- VernacularTitle:甘露糖结合蛋白基因多态性在IgA肾病肾组织免疫沉积多样性形成中的作用
- Author:
Rujun GONG
1
;
Zhihong LIU
;
Zhaohong CHEN
;
Dong LIU
;
Leishi LI
Author Information
1. Research Institute of Nephrology Jinling Hospital School of Medicine Nanjing University
- From:
Chinese Journal of Medical Genetics
2001;18(2):83-87
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the relationship between mannose-binding protein (MBP) gene codon 54 (GGC/GAC) polymorphism and the patterns of glomerular immune deposition in IgA nephropathy (IgAN) and explore its functional significance. Methods IgAN patients were divided into two groups according to the pattern of glomerular immune deposition. Group A included 77 patients with glomerular IgA and C3 deposits. Group AGM consisted of 70 patients with glomerular IgA, IgG, IgM, C3 and C1q deposits. One hundred and forty healthy adults were used as normal controls. MBP genotypes were investigated by PCR-RFLP. Serum MBP levels of some subjects with different genotypes were also assayed by ELISA simultaneously. Results The genotype frequency of GAC heterozygotes was significantly higher in group AGM than in group A (41.4% vs. 19.5%, P<0.01) or normal subjects (41.4% vs. 26.4%, P<0.05), while no difference was found in the distribution of MBP genotypes between group A and normal subjects. The allele frequency of GAC mutation was also higher in group AGM than in group A (0.236 vs. 0.136, P<0.05) or normal subjects (0.236 vs. 0.146, P<0.05). The variant allele (GAC) was markedly associated with group AGM (OR=1.95, 95%CI:1.06-3.58). In both group A and group AGM, more patients carrying the variant allele had episodes of upper respiratory or gastrointestinal infections prior to the onset or exacerbation of IgAN than wild homozygotes. In addition, a significant difference in serum MBP level was also observed among the three genotypes (GGC/GGC>GGC/GAC>GAC/GAC) (P<0.0001) for all groups, while there were no differences in serum MBP levels for subjects with the same genotypes among the three groups(P>0.05). Conclusion The above findings provide evidence that IgAN patients with abundant immune deposits in glomeruli show a higher frequency of MBP gene variation which is associated with a high frequency of infection and a low serum MBP level. This genetic deficiency may lead to an impaired first-line defense and a less effective clearance of immune complex than those without this mutation and thereafter accelerate glomerular immune deposition during the process of disease.
