Atopy and asthma: genetic variants of IL-4 and IL-13 signalling

Shirakawa, Taro; Deichmann, Klaus A.; Izuhara, Kenji; Mao, Xiao-Quan; Adra, Chaker N.; Hopkin, Julian M.

doi:10.1016/s0167-5699(99)01492-9

Cited by 255 publications

(199 citation statements)

References 29 publications

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“…To our knowledge, no studies have been done to date on the genetics of the IL-4R gene in RA or JIA patients. Data from a functional study (Shirakawa et al, 2000;Hershey et al, 1997) showed that the R551 variant is associated with increased IL-4 receptor signalling and increased total IgE levels. These results indicate that the R551 polymorphism is associated with differentiation of the immune profile into a Th2 type response.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women

Suppiah

Rooney

Vandenbroeck

2006

Experimental and Molecular Pathology

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Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women. Suppiah, V., Rooney, M., & Vandenbroeck, K. (2006). Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women. AbstractRheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with polygenic autoimmune background. We analysed the IL-4 +33 C/T and IL-4R Q551R single nucleotide polymorphisms (SNPs) in 294 RA, 72 JIA and 165 controls from Northern Ireland. Analysis of the individual phenotypes (RA or JIA) showed that both the IL-4 +33 TT (P = 0.02; OR: 0.25, 95% CI: 0.07-0.87) and the IL-4R Q551R CC genotypes (P = 0.001; OR: 0.19, 95% CI: 0.06-0.56) were exclusively decreased in female RA patients compared to female controls. Similar non-significant trends were observed in female JIA patients (OR: 0.25, 95% CI: 0.03-2.11 and OR: 0.31, 95% CI: 0.07-1.47, respectively). Analysis of the common phenotype (inflammatory arthropathy; i.e. JIA and RA combined) corroborated the unique association of these polymorphisms with female inflammatory arthropathy (P = 0.013 and 0.002, respectively). This is the first demonstration of sex-specific association of the two foremost genes of the IL-4 signalling cascade with chronic inflammatory arthropathies.

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Section: Discussionmentioning

confidence: 99%

Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women

Suppiah

Rooney

Vandenbroeck

2006

Experimental and Molecular Pathology

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“…14 -26 In addition, the gene encoding the IL-4 receptor (IL-4R) ␣ subunit is polymorphic. 27 A novel IL-4 receptor ␣ allele in which a G-to-A substitution at position 1902 results in a change from glutamine to arginine at position 551 in the IL-4R␣ protein has been identified, with the variant allele associated with enhanced signalling activity 28 and more common in patients with atopy. 29 The potential role of immune mechanisms in the pathogenesis of diclofenac-induced hepatotoxicity has been explored in this study.…”

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confidence: 99%

Hepatic adducts, circulating antibodies, and cytokine polymorphisms in patients with diclofenac hepatotoxicity

et al. 2004

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Diclofenac is a nonsteroidal anti-inflammatory drug that causes rare but serious hepatotoxicity, the mechanism of which is unclear. The purpose of the present study was to explore the potential role played by the immune processes. Antibodies to diclofenac metabolite-modified liver protein adducts were detected in the sera of seven out of seven patients with diclofenac-induced hepatotoxicity, 12 of 20 subjects on diclofenac without hepatotoxicity, and none of four healthy controls. The antibodies recognized adducts expressed in livers from rats treated with multiple doses of diclofenac, but not in those given single doses. In addition, several potential diclofenac adducts were identified in the liver of a patient with diclofenac-induced hepatic failure, but not from a normal human donor liver, by immunoblotting with an adduct-selective rabbit antiserum. To determine whether or not polymorphisms in genes encoding cytokine-related proteins influence susceptibility to hepatotoxicity, genotyping for the polymorphisms -627 in the interleukin (

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“…22 Changes to aminoacid residues, including the Gln576Arg polymorphism, are functionally important and impact the signaling cascade by the engaged receptor, 23 and IL4R SNPs are associated with susceptibility to immune-related diseases including asthma, atopy and type I diabetes. [24][25][26] One consideration in this study is that we made no attempts to correct for multiple comparisons, although we conducted several tests. First, MDR itself is protected from multiple comparisons as permutation testing is conducted at the end of an MDR analysis, only on the best model at each level of interaction.…”

Section: Discussionmentioning

confidence: 99%

Multifactor dimensionality reduction reveals gene–gene interactions associated with multiple sclerosis susceptibility in African Americans

et al. 2006

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Atopy and asthma: genetic variants of IL-4 and IL-13 signalling

Cited by 255 publications

References 29 publications

Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women

Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women

Hepatic adducts, circulating antibodies, and cytokine polymorphisms in patients with diclofenac hepatotoxicity

Multifactor dimensionality reduction reveals gene–gene interactions associated with multiple sclerosis susceptibility in African Americans

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