Association of IgA nephropathy with T-cell receptor constant alpha chain gene polymorphism

Li, Philip Kam-Tao; Poon, P.W.F.; Phil, M.; Poon, Angela S.Y.; Szeto, Cheuk‐Chun; Yu, Alan C. L.; Lai, Kar Neng

doi:10.1016/s0272-6386(97)90061-5

Cited by 13 publications

(8 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently, several investigators reported that polymorphisms of the genes for the T cell receptor α chain (Deenitchina et al 1999;Li et al 1997), the β chain (Nagasawa et al 1995), the IgA1 heavy chain switch region (Demaine et al 1988;Moore et al 1990), and Iα1 germ-line transcript regulation (Yano et al 1998) are associated with IgA nephropathy. In this study, we have found that a specific distribution of polymorphisms of the FcαR gene is present in IgA nephropathy compared with not only healthy adults, but also patients with other primary GN.…”

Section: Discussionmentioning

confidence: 99%

Polymorphism in promoter region of Fcα receptor gene in patients with IgA nephropathy

et al. 2001

View full text Add to dashboard Cite

We have recently identified two novel polymorphisms (-114T/C and +56T/C relative to the major transcription start site) in the functional promoter region of the Fcalpha receptor (FcalphaR) gene. Since altered FcalphaR expression may be associated with IgA nephropathy, we examined these promoter polymorphisms in this disease. Patients with IgA nephropathy (n = 90), patients with other primary glomerulonephritis (n = 50), and healthy adults (n = 83) were studied. Genotyping was performed by the polymerase chain reaction (PCR) followed by direct sequence analysis and was subsequently confirmed by PCR with mismatched primers followed by restriction fragment length polymorphism analysis. The study demonstrated that the frequency of the +56C allele in patients with IgA nephropathy (0.511) was significantly (P < 0.01) higher than that in patients with other primary glomerulonephritis (0.350) and healthy adults (0.337). In addition, a significant increase in the frequency of the +56CC genotype was observed in patients with IgA nephropathy (27.8% vs 10.0% in other GN and vs 9.6% in healthy adults). In contrast, no significant difference in the frequencies of the +56CC genotype and +56C allele was observed between other primary glomerulonephritis patients and healthy adults. The frequency of the -114CC genotype in patients with IgA nephropathy was significantly increased compared with those in both control groups (15.6% vs 4.0% in other GN and vs 2.4% in healthy adults). Polymorphisms of the FcalphaR promoter region therefore appear to be associated with susceptibility to IgA nephropathy, suggesting the importance of the FcalphaR gene and its expression in this disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Polymorphism in promoter region of Fcα receptor gene in patients with IgA nephropathy

et al. 2001

View full text Add to dashboard Cite

show abstract

“…16,17 This prompted us to resequence and further analyze the gene. Our case-control and family-based analyses with haplotypes and multiple SNPs clearly support the notion that the overtransmitted/observed haplotypes and multiple SNPs confer risk to IgAN, and, conversely, that the undertransmitted/observed haplotypes and multiple SNPs protect from IgAN.…”

Section: Discussionmentioning

confidence: 99%

“…Among these, SNP 1 (previously reported Ϫ575 A/G) was the locus that previous controversial restriction fragment length polymorphism results were based on. 16,17 Logistic regression analysis with adjustment for age and gender demonstrated all eight SNPs (SNPs 1 to 8) were significantly associated with IgAN (Table 1). After Bonferroni correction for multiple tests (corrected for eight tests), SNPs 1 to 6 remained significant ( Table 1).…”

Section: Single Snp Association Testsmentioning

confidence: 99%

See 1 more Smart Citation

TRAC Variants Associate with IgA Nephropathy

Xue

et al. 2009

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

The T cell receptor alpha constant gene (TRAC) encodes the constant region of the ␣ chain for the T cell receptor, and the association of its gene variants with IgA nephropathy remains controversial. The authors resequenced the gene in 100 patients with IgA nephropathy and 100 controls, tested its linkage disequilibrium pattern, constructed haplotypes, and performed association and functional studies. First, the association between TRAC variants and IgA nephropathy was tested in 704 patients and 704 controls. Next, these 704 patients were divided into two independent datasets-310 with family member(s) and 394 single patients-to test the association separately. Results showed that the gene is located in a recombination hot spot, with nine linkage disequilibrium blocks within a 6.9-kb region. There is a hypervariable region with six single-nucleotide polymorphisms (SNPs) in an 85-bp stretch in intron 1. We identified multiple SNPs and two haplotypes that associate with IgA nephropathy (P ϭ 0.0000013-0.0096 by logistic regression for SNPs; P ϭ 0.0003 and P ϭ 0.0398 for haplotype associations). The family-based study replicated both haplotype findings, and the 394 single-patient case-control study replicated the association with haplotype 1 (P ϭ 0.0033). The overtransmitted/observed haplotypes demonstrated reduced transcription activity compared with the undertransmitted/observed haplotypes. In conclusion, this study suggests an association between TRAC variants and susceptibility to IgA nephropathy.

show abstract

“…In patients with IgAN, Li et al found more Taq1 alleles than in normal controls but no relationship to renal functions [41]. In contrast, Deenitchina et al [42]found genotypic frequency did not differ with that in normal controls, but those patients with progressive renal failure more commonly (odds ratio 2.7) had the Taq1 allele (TT or tT genotype).…”

Section: Iga Immune Systemmentioning

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

Association of IgA nephropathy with T-cell receptor constant alpha chain gene polymorphism

Cited by 13 publications

References 16 publications

Polymorphism in promoter region of Fcα receptor gene in patients with IgA nephropathy

Polymorphism in promoter region of Fcα receptor gene in patients with IgA nephropathy

TRAC Variants Associate with IgA Nephropathy

Molecular Genetics in IgA Nephropathy

Contact Info

Product

Resources

About