Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the switch regions of Ig heavy chain genes of patients with IgA glomerulonephritis (IgA-GN) using restriction fragment length polymorphism (RFLP) analysis. Genomic DNA from patients and controls was digested with the restriction endonuclease Sst I and transferred to nylon membranes using the Southern blot procedure and hybridized with a probe homologous to the switch region of the Ig C mu gene (S mu) which detects RFLPs in both S mu and the switch region of the Ig C alpha 1 gene (S alpha 1). A significant decrease in the frequency of the 2.6;2.1 kb heterozygous S mu phenotype was found in patients with IgA-GN (P = 0.003). With respect to the S alpha 1 region, there was a significant increase in the frequency of the 7.4 kb S alpha 1 phenotype (P = 0.002). In addition, a significant increase in the frequency of the 7.4 kb S alpha 1 allele was found (P = 0.0002). These results suggest that gene(s) within the Ig heavy chain loci may be important in the pathogenesis of IgA-GN.
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PMID:Relation of mesangial IgA glomerulonephritis to polymorphism of immunoglobulin heavy chain switch region. 289 61

A molecular analysis of HLA class II genes was undertaken in order to characterize the previously reported association between HLA-DR2 and glomerulonephritis caused by antibodies to glomerular basement membrane (Goodpasture's disease). Genomic DNA was prepared from 53 patients with Goodpasture's disease and analysed by: (i) Southern blotting using cDNA probes to DRB, DQA and DQB genes, after digestion with TaqI endonuclease; (ii) allele-specific oligonucleotide probing of specifically amplified DNA; and (iii) nucleotide sequencing of relevant alleles. The patients had a greatly increased frequency of DRw15 (a subspecificity of DR2) which was present in 75.5% of patients and 31% of controls (p < 0.0001). The frequency of DR4 was also increased, especially in patients without DRw15. Overall, 90.5% of the patients had either DRw15 or DR4. In contrast, the frequency of DR1 was significantly reduced (patients 5.6%, controls 20.7%, p < 0.01). Differences in the frequencies of DQA and DQB alleles could all be explained by linkage disequilibrium. Nucleotide sequences of relevant alleles were identical to those previously published. Comparison of derived amino acid sequences of expressed DR beta chains showed that the DR beta chains of DRw15 and DR4 shared a six-amino-acid motif from positions 26-31, that included four polymorphic amino acids none of which are shared with DR1. A sequence-specific oligonucleotide detected this amino-acid motif in 45/49 (91.8%) patients tested. Thus, this particular motif, which lies on the floor of the antigen binding groove, has a stronger association with Goodpasture's disease than any individual allele, and may be of pathogenic significance.
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PMID:Molecular analysis of HLA class II genes in Goodpasture's disease. 770 68

End-stage renal disease (ESRD) involves an inflammatory process. Interleukin-1 receptor antagonist (IL-1Ra) and interleukin-1beta gene polymorphisms affect susceptibility to the disease in several inflammatory diseases. We investigated whether these polymorphisms are involved in ESRD by genotyping DNA from 602 dialyzed patients and 433 controls with polymerase chain reaction and digestion with restriction endonuclease. Allele 2 of the IL-1Ra VNTR polymorphism was associated with ESRD (OR=1.46, 95% CI 1.19-1.78). We also found a strong association between this allele and recurrent peritonitis in peritoneal dialysis patients. Odds ratio for the risk allele was higher compared to entire ESRD group (OR=3.6, 95% CI 1.70-7.44). The homozygosity for the allele 2 was associated with disease progression, especially in patients with diabetic nephropathy and glomerulonephritis. For the patients from these two subgroups having 2.2 genotype, the mean time from disease onset to ESRD was 1.5 and 2.2 years, respectively, compared to 6.4 and 9.8 years for those with 1.1 genotype. The IL-1Ra allele 2 is associated with ESRD in our dialyzed patients. Our results demonstrate for the first time the association of the IL-1Ra allele 2 with faster progression to ESRD. If confirmed in other populations, it might be a predictor of faster disease progression.
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PMID:Interleukin-1 receptor antagonist gene polymorphism affects the progression of chronic renal failure. 1722 77

Interleukin-6 (IL-6) is a multifunctional cytokine produced by different cell types, including monocytes, lymphocytes, endothelial and mesangial cells. Deregulated production of IL-6 was found to be involved in mesangial proliferative glomerulonephritis. We investigated whether the single nucleotide polymorphism (SNP) in the promoter region of the IL-6 gene is associated with a development of chronic glomerulonephritis (CGN). The study group consisted of 541 patients with CGN. Of those 338 already progressed to ESRD. The control group involved 253 healthy individuals. All subjects were genotyped for the -634 C/G polymorphism of the IL-6 gene by polymerase chain reaction (PCR). PCR product was digested with BsrBI restriction endonuclease and analyzed on 3% agarose. The allele and genotype frequencies were similar between CGN patients in a pre-dialysis stage and control subjects. Significantly increased frequency of the G allele was observed in the ESRD patients (13% vs. 6% in pre-dialysis stage, P < 0.01). After dividing ESRD patients according to time from reported disease onset to ESRD, those with time < or =5 years showed even higher G allele frequency (21% vs. 13% in entire ESRD group). Interestingly, most of the GG homozygotes were in this faster progressing group. Both subgroups were comparable for sex, age, BMI, total cholesterol and serum creatinine. The multivariate logistic regression analysis revealed that the IL-6 genotype with the G allele was an independent risk factor of progression to ESRD (P < 0.001). Our results indicate that the IL-6 -634 G/C polymorphism may be a possible risk factor for faster progression of chronic glomerulonephritis to ESRD. It is also possible that this polymorphism is in linkage disequilibrium with another functional polymorphism in the II-6 gene or its vicinity.
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PMID:Interleukin-6 gene polymorphism and faster progression to end-stage renal failure in chronic glomerulonephritis. 1765 29

Microbial nucleic acid recognition serves as the major stimulus to an antiviral response, implying a requirement to limit the misrepresentation of self nucleic acids as non-self and the induction of autoinflammation. By systematic screening using a panel of interferon-stimulated genes we identify two siblings and a singleton variably demonstrating severe neonatal anemia, membranoproliferative glomerulonephritis, liver fibrosis, deforming arthropathy and increased anti-DNA antibodies. In both families we identify biallelic mutations in DNASE2, associated with a loss of DNase II endonuclease activity. We record increased interferon alpha protein levels using digital ELISA, enhanced interferon signaling by RNA-Seq analysis and constitutive upregulation of phosphorylated STAT1 and STAT3 in patient lymphocytes and monocytes. A hematological disease transcriptomic signature and increased numbers of erythroblasts are recorded in patient peripheral blood, suggesting that interferon might have a particular effect on hematopoiesis. These data define a type I interferonopathy due to DNase II deficiency in humans.
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PMID:Type I interferon-mediated autoinflammation due to DNase II deficiency. 2925 62