Familial occurrence of primary glomerulonephritis: evidence for a role of genetic factors

Scolari, Francesco; Amoroso, Antonio; Savoldi, Silvana; Prati, E.; Scaini, Patrizia; Manganoni, Annunciata; Borelli, I; Mazzola, Gina; Canale, L.; Sacchi, G; Miglietti, Nunzia; Cristinelli, L; Curtoni, E. S.; Binda, P. L.; Bonomelli, D.; Maiorca, R

doi:10.1093/ndt/7.7.587

Cited by 32 publications

(22 citation statements)

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“…The existence of IgM N as a distinct clinical entity has long been a matter of controversy, and HLA association studies in IgM N are scarce. Scolari et al [40, 41] reported two studies about familial IgM N; they did not find any associated HLA loci even after an extended haplotype and restriction fragment length polymorphism comparison within these families. In our study, increased frequencies of DQB1- 0401 were observed in the IgM N group as compared with the MCNS group.…”

Section: Discussionmentioning

confidence: 99%

HLA-DR, -DQB Typing of Steroid-Sensitive Idiopathic Nephrotic Syndrome Children in Taiwan

Huang

Lin

et al. 2009

Nephron Clin Pract

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Background: The association between human leukocyte antigens (HLA) and idiopathic nephrotic syndrome (INS) in children has been discussed in various studies. Methods: In this study, 59 Chinese children with steroid-sensitive nephritic syndrome (SSNS) in Taiwan were enrolled, and 33 patients underwent renal biopsy. Results: The frequency of HLA-DR11 was found to be significantly higher and HLA-DR14 was lower in SSNS patients as compared with the healthy control group. In frequent relapsers, HLA-DR4 was more frequent, while HLA-DQB1*0602 was less frequent, as compared with infrequent relapsers. However, there was no significant difference between steroid-dependent and non-steroid-dependent patients. In patients who showed a response to levamisole, the HLA-DR9 and -DQB1*0303 alleles were more frequent, while HLA-DR13 was less frequent. In a comparison of HLA in different INS pathologies, HLA-DQB1*0401 was significantly frequent in IgM nephropathy. Even though we compared each group with the control group separately, the HLA distributions of both groups still differed from each other. Our data suggest that the immunogenic characteristics of children with SSNS in Taiwan are different from those of other populations. The common motif between different HLA alleles and the three-dimensional crystal structures may offer an explanation for the varying results from different populations. Conclusion: According to HLA typing, the results support the hypothesis that IgM nephropathy is a different entity from minimal change nephrotic syndrome.

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Section: Discussionmentioning

confidence: 99%

HLA-DR, -DQB Typing of Steroid-Sensitive Idiopathic Nephrotic Syndrome Children in Taiwan

Huang

Lin

et al. 2009

Nephron Clin Pract

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“…Four kindreds in the US were from Kentucky, one was from Connecticut and one was from Washington State. Eighteen kindreds have been reported 9,[12][13][14][15][16] ; the relationship of these kindreds to those reported previously is indicated ( Genetic analysis. We prepared genomic DNA from venous blood of kindred members as described 25 .…”

Section: Methodsmentioning

confidence: 99%

IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22–23

et al. 2000

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End-stage renal disease (ESRD) is a major public health problem, affecting 1 in 1,000 individuals and with an annual death rate of 20% despite dialysis treatment. IgA nephropathy (IgAN) is the most common form of glomerulonephritis, a principal cause of ESRD worldwide; it affects up to 1.3% of the population and its pathogenesis is unknown. Kidneys of people with IgAN show deposits of IgA-containing immune complexes with proliferation of the glomerular mesangium (Fig. 1). Typical clinical features include onset before age 40 with haematuria and proteinuria (blood and protein in the urine), and episodes of gross haematuria following mucosal infections are common; 30% of patients develop progressive renal failure. Although not generally considered a hereditary disease, striking ethnic variation in prevalence and familial clustering, along with subclinical renal abnormalities among relatives of IgAN cases, have suggested a heretofore undefined genetic component. By genome-wide analysis of linkage in 30 multiplex IgAN kindreds, we demonstrate linkage of IgAN to 6q22-23 under a dominant model of transmission with incomplete penetrance, with a lod score of 5.6 and 60% of kindreds linked. These findings for the first time indicate the existence of a locus with large effect on development of IgAN and identify the chromosomal location of this disease gene.

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“…Previous studies reported a higher risk of identical twins to IgAN and several cases of familial IgAN (7,8). Of note, linkage analysis of familial IgAN revealed a close association with the trait 6q22-23 (IGAN1) in this disease (9), although no proteins coded by IGAN1 have been identified.…”

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confidence: 89%

Genome-Wide Scan in a Novel IgA Nephropathy Model Identifies a Susceptibility Locus on Murine Chromosome 10, in a Region Syntenic to Human IGAN1 on Chromosome 6q22–23

Suzuki¹,

Suzuki²,

Yamanaka³

et al. 2005

Journal of the American Society of Nephrology

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Genetic factors are considered to be involved in the initiation and progression of IgA nephropathy (IgAN) on the basis of racial differences in the prevalence and familial aggregation. The ddY mouse is a spontaneous animal model of human IgAN, with a highly variable incidence and extent of glomerular injury as a result of the heterogeneous background, resembling the human situation. It was hypothesized that susceptibility genes for IgAN can be detected by a genome-wide scan using this model. First, serial renal biopsies were performed at 20, 40, and 60 wk of age in 361 ddY mice. The ddY mice were classified into three groups on the basis of the onset of glomerular injury: Early onset at 20 wk (31.9%), late onset at 40 wk (37.9%), and quiescent even at 60 wk (30.2%). The severity of glomerular lesions in both onset groups correlated with the intensity of glomerular IgA deposition but not with serum IgA level. The genome-wide scan with 270 microsatellite markers identified three chromosomal regions on chromosomes 1, 9, and 10, which were significantly associated with the glomerular injuries. Surprisingly, the peak marker D10MIT86 on chromosome 10 is located on the region syntenic to human 6q22-23 with IGAN1, which is the responsible candidate of familial IgAN. In addition, D1MIT16 on chromosome 1 was very closely located at the locus of selectin gene, which is a known candidate of human IgAN. In conclusion, the three-group ddY mouse model can be a useful tool for identifying the susceptibility genes and also to examine their roles in the pathogenesis of IgAN.

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Familial occurrence of primary glomerulonephritis: evidence for a role of genetic factors

Cited by 32 publications

References 0 publications

HLA-DR, -DQB Typing of Steroid-Sensitive Idiopathic Nephrotic Syndrome Children in Taiwan

HLA-DR, -DQB Typing of Steroid-Sensitive Idiopathic Nephrotic Syndrome Children in Taiwan

IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22–23

Genome-Wide Scan in a Novel IgA Nephropathy Model Identifies a Susceptibility Locus on Murine Chromosome 10, in a Region Syntenic to Human IGAN1 on Chromosome 6q22–23

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