Complement 4 Locus II Gene Deletion and DQA1*0301 Gene: Genetic Risk Factors for IgA Nephropathy and Henoch-Schönlein Nephritis

Jin, Dong Kyu; Kohsaka, Takao; Koo, Ja Wook; Ha, Il Soo; Cheong, Hae Il; Choi, Yong

doi:10.1159/000189098

Cited by 27 publications

(14 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, patients had a greater frequency of a C4 homozygous null phenotype. This finding was subsequently confirmed in Japanese 26 and Korean 27 patients. In the Japanese group, serum C4 concentrations were significantly lower in patients with C4 gene deletion than in patients without the deletion.…”

Section: Human Leucocyte Antigen Genessupporting

confidence: 54%

Gene polymorphism in IgA nephropathy

Tang

Lai

2001

Nephrology

View full text Add to dashboard Cite

SUMMARY: IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. Since its original description in 1968, a large body of clinical, epidemiological and immunological studies of its pathogenesis has emerged. However, the basic molecular mechanisms of abnormal mesangial IgA deposition have remained obscure. In recent years, much clinical and experimental evidence has indicated the presence of genetic factors in the development and progression of IgAN. The search for susceptibility loci has centred on the major histocompatibility complex (MHC) using disease association in family and population studies. In addition, genes outside the realm of the MHC have been reported. The evidence for genetic factors in the onset and progression of IgAN is reviewed in this paper. The major loci influencing disease susceptibility include HLA‐DR4, ‐DQw7 and ‐DQβ, C4 null and T‐cell receptor Cα genes, whereas those affecting the natural course of IgAN include HLA‐DQβ, angiotensin‐converting enzyme D/D, T‐cell receptor Cβ and endothelial cell nitric oxide synthase 4a alleles.

show abstract

Section: Human Leucocyte Antigen Genessupporting

confidence: 54%

Gene polymorphism in IgA nephropathy

Tang

Lai

2001

Nephrology

View full text Add to dashboard Cite

show abstract

“…The implication of HLA class II genes in the susceptibility to HSP has previously been described [10][11][12][13][14]. Although multiple genetic and environmental factors are considered to be involved in the pathogenesis of HSP, factors other than HLA remain to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…Susceptibility to HSP has been observed in Italian and Spanish patients who carried human leukocyte antigen (HLA)-DRB1*01 and DRB1*11. Some evidence suggests that the disease is multifactorial, with both environmental and genetic factors contributing to its pathogenesis [10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

CTLA-4 +49 A/G genotype and HLA-DRB1 polymorphisms in Turkish patients with Henoch–Schönlein purpura

et al. 2008

View full text Add to dashboard Cite

The pathogenesis of Henoch-Schönlein purpura (HSP) remains unknown; however, it is generally considered to be an immune complex-mediated disease. Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is expressed on activated T cells, and, thus, it is critically involved in the immune response. We aimed to investigate the possible influence of CTLA-4 polymorphisms for susceptibility to HSP and determine if there were associations with human leukocyte antigen (HLA)-DRB1 genotypes. Using polymerase chain reaction-based DNA genotyping, we investigated the polymorphisms located in the genes encoding CTLA-4 in 100 patients with HSP and 156 ethnically matched healthy controls. When CTLA-4 +49 A/G polymorphism of HSP patients and control group was compared, no associations with joint, gastrointestinal or renal manifestations, or susceptibility to HSP, were observed. However, patients with nephrotic proteinuria had higher HLA-DRB1*13 positivity [odds ratio (OR) = 3.76, 95% confidence interval (95%CI) = 1.25-11.23, P = 0.025]. When the patients were stratified according to CTLA-4 polymorphism, a significant association between nephrotic proteinuria patients and carriage of the AG genotype was also found (OR = 15.42, 95%CI = 1.59-148.82, P = 0.008). These results suggested that CTLA-4 +49 A/G polymorphism does not contribute to susceptibility to HSP; however, the presence of CTLA-4 AG genotype and HLA-DRB1*13 could be a risk factor for developing nephrotic-range proteinuria in these patients.

show abstract

“…Deletion of the locus II for C4 and not the C4B sequence was shown to be a risk factor; the deleted gene could be either C4A and C4B. However, because DQ A1*0301 was more frequent, either could be a risk factor for IgAN [27]. In IgAN, C3 is expressed in proximal tubule cells and occasionally in glomerular crescents and correlates with proteinuria, glomerulosclerosis, and interstitial fibrosis; controls for other glomerular diseases were not reported [28].…”

Section: Complementmentioning

confidence: 99%

Molecular Genetics in IgA Nephropathy

Galla¹

2001

Nephron

View full text Add to dashboard Cite

Evidence from both genotypic and phenotypic perspectives is considered that patients may be genetically predisposed to IgA nephropathy (IgAN) or Henoch-Schönlein purpura (HSP) or that a factor(s) might exclusively contribute to their progression to chronic renal failure. In contrast to most other renal diseases, both IgAN and HSP are uncommon in blacks; this is unexplained but is not due to their low frequency of the A2m(1) allotype. The association of these diseases or their progression with a variety of abnormalities of IgA immunobiology in patients and their families has not been linked to any genotype; similarly, no HLA antigen has been positively or negatively associated in any consistent way. Although complement factor 3 universally accompanies IgA glomerular deposition, complement pathway abnormalities are only sporadically reported with either IgA deposition or disease progression. Whether angiotensin-related polymorphism including the converting enzyme alleles have a specific predictable role, particularly in the progression of renal failure in IgAN, remains problematic. The promising possibility that a structural defect in IgA1 due to an as yet unidentified genetic defect accounts for the deposition of IgA is considered in some detail. Nevertheless, the genetic mechanism(s) of progressive renal failure, whether exclusive to IgAN or to glomerular diseases generally, is of paramount importance.

show abstract

Complement 4 Locus II Gene Deletion and DQA1*0301 Gene: Genetic Risk Factors for IgA Nephropathy and Henoch-Schönlein Nephritis

Cited by 27 publications

References 17 publications

Gene polymorphism in IgA nephropathy

Gene polymorphism in IgA nephropathy

CTLA-4 +49 A/G genotype and HLA-DRB1 polymorphisms in Turkish patients with Henoch–Schönlein purpura

Molecular Genetics in IgA Nephropathy

Contact Info

Product

Resources

About