Interleukin-1 cluster gene polymorphisms in childhood IgA nephropathy

Abstract

We have carried out a study with the aim of investigating the association between single nucleotide polymorphisms (SNPs) of the IL-1 gene cluster and childhood IgA nephropathy (IgAN). SNPs of the IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist (RN) genes (IL1A, IL1B, and IL1RN, respectively) were analyzed in 182 patients with childhood IgAN and in 500 healthy controls. The IgAN patients were also dichotomized and compared with respect to proteinuria (<4 mg and >or=4 mg/m(2) per hour, respectively), the presence or absence of podocyte foot process effacement, and the presence of pathologically early and advanced disease markers, such as interstitial fibrosis, tubular atrophy, or global sclerosis. Significant differences in SNP frequencies were observed for the IL1B and IL1RN genes (rs1143627, rs3917356, and rs1143633 in the IL1B gene, and rs928940, rs439154, and rs315951 in the IL1RN gene). Moreover, rs1143627, rs3917356, and rs1143633 of IL1B were found to be significantly associated with the presence of podocyte foot process effacement. Our results suggest that the IL1B and IL1RN genes are associated with increased susceptibility to IgAN in children. They also suggest that the development of proteinuria in IgAN is related to IL1A and that podocyte foot process effacement is associated with IL1B.

Association between toll-like receptor 10 (TLR10) gene polymorphisms and childhood IgA nephropathy

“…iconcologia.net/index.php) were used. The associations between genotypes of SNPs and risk of IgAN were estimated by computing the odds ratios (ORs) and their 95% confidence intervals (CIs) with logistic regression analyses, controlling for gender as a covariable [10]. In logistic regression analysis for each SNP, models assuming either codominant inheritance (that is, the relative hazard differed between subjects with one minor allele and those with two minor alleles), dominant inheritance (that is, subjects with one or two minor alleles had the same relative hazard for the disease), or recessive inheritance (that is, only subjects with two minor alleles were at increased risk of the disease) were used.…”

“…All IgAN patients with prolonged hematuria or concomitant proteinuria were examined by kidney biopsy. IgAN patients were divided according to presence or absence of proteinuria at kidney biopsy (>4 mg/m 2 /h) [10,11], gross hematuria episodes as an initial symptom of IgAN, and advanced pathological disease markers (interstitial fibrosis, tubular atrophy, or global sclerosis), respectively. The control group was recruited from subjects visiting the hospital for routine health checkups.…”

Cytokines of the Immune System

“…17 The susceptibility to alopecia areata seems to be associated with the IL1A gene polymorphism rs3783553 in two independent Chinese populations. 18 This is an insertion/deletion polymorphism (ttca/-) at miRNA-122 binding site in the 3 ′ untranslated region that was shown to be functional.…”

Novel genes and variants associated with IgA nephropathy by co-segregating with the disease phenotypes in 10 IgAN families

“…CARD8 suppresses NF-κB activation (Bouchier-Hayes et al, 2001) and the proinflammatory protease caspase-1 (Razmara et al, 2002). The latter regulates IL-1beta, which is associated with tubulointerstitial fibrosis and the progression of IgAN (Myllymaki et al, 2007;Hahn et al, 2009;Stangou et al, 2013). Our study is the first to show a possible association of this gene with IgAN.…”