Identification of a novel single‐nucleotide polymorphism (Val554Ile) and definition of eight common alleles for human <i>IL4RA</i> exon 11

Lozano, Francisco; Places, Lourdes; Vila, Josep M.; Padilla, Olga; Arman, Mehmet; Gimferrer, Idoia; Suarez, Brian K.; Iglesia, A. López de la; Miserachs, N.; Vives, Jordi

doi:10.1034/j.1399-0039.2001.057003216.x

Cited by 11 publications

(5 citation statements)

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“…Genetic association studies are often difficult to interpret due to poor reproducibility in different populations [ 39 , 40 ]. This may well result, among other reasons, from the fact that these studies are focused only on one SNP [ 18 , 26 , 27 ] and that penetrance of the alleles may be influence by other factors [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…The IL4RA gene is located on chromosome 16p (16p12.1) [ 14 ], a region reported in linkage with atopy in different populations [ 15 , 16 ]. Several single-nucleotide polymorphisms (SNPs) have been identified in the coding region of the IL4RA gene, many of them resulting in aminoacid substitutions [ 17 , 18 ]. One of these polymorphisms, 576Q>R, consists of an A-to-G transition at nucleotide 1902, causing a change from glutamine to arginine at codon 576 (Q576R) in the cytoplasmic domain of the IL-4Rα.…”

Section: Introductionmentioning

confidence: 99%

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Interleukin-4 (IL4) and Interleukin-4 receptor (IL4RA) polymorphisms in asthma: a case control study

et al. 2005

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BackgroundIL4/IL4RA pathway plays an important role in atopy and asthma. Different polymorphisms in IL4 and IL4RA genes have been described. Particularly, -33C>TIL4 and 576Q>RIL4RA SNPs have been independently associated to atopy and asthma. The purpose of this study was to analyse these polymorphisms in a population of patients with a well-characterized asthma phenotype.MethodsA total of 212 unrelated Caucasian individuals, 133 patients with asthma and 79 healthy subjects without symptoms or history of asthma or atopy and with negative skin prick tests were recruited. Lung function was measured by spirometry and asthma was specialist physician-diagnosed according to the ATS (American Thoracic Society) criteria and classified following the GINA (Global Initiative for Asthma) guidelines. Skin prick tests were performed according to EAACI recommendations. -33C>TIL4 was studied with TaqMan assay and 576Q>RIL4RA by PCR-RFLP technique. Hardy-Weinberg equilibrium was analysed in all groups. Dichotomous variables were analysed using χ2, Fisher exact test, Monte Carlo simulation test and odds ratio test. To model the effects of multiple covariates logistic regression was used.ResultsNo statistically significant differences between the group of patients with asthma and the controls were found when the allele and genotype distribution of -33C>TIL4 and 576Q>RIL4RA polymorphisms were compared. However, the T allele of the -33C>TIL4 SNP was more frequent in patients with persistent asthma. Multivariate analysis adjusted for age and sex confirmed that carriers of allele T had an increased risk of persistent asthma (OR:2.77, 95%CI:1.18–6.49; p = 0.019). Analysis of combination of polymorphisms showed that patients carrying both the T allele of -33C>TIL4 and the A allele of 576Q>RIL4RA had an increased risk of asthma. This association was particularly observed in persistent asthma [Fisher's p value = 0.0021, Monte Carlo p value (after 104 simulations) = 0.0016, OR:3.39; 95% CI:1.50–7.66].ConclusionOur results show a trend of association between the genetic combination of the T allele of -33C>TIL4 and the A allele of 576Q>RIL4RA with asthma. This genetic variant was more frequently observed in patients with persistent asthma. As long as this study was performed in a small population, further studies in other populations are needed to confirm these results.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interleukin-4 (IL4) and Interleukin-4 receptor (IL4RA) polymorphisms in asthma: a case control study

et al. 2005

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“…In the IL4RA gene, located in the shorter arm of chromosome 16, a number of SNPs have been reported. [13][14][15][16][17][18][19] Among others, the T/C base exchange at +22446 (known as cys406arg) in exon 9 of the IL4RA gene (resulting in an amino acid substitution of cysteine for arginine) has been associated with atopy. In some studies, the common allele T-ie, coding for cysteinewas found to predispose subjects to atopy.…”

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confidence: 99%

Epistatic effect of IL1A and IL4RA genes on the risk of atopy

Ådjers

Karjalainen

Hurme

2004

Journal of Allergy and Clinical Immunology

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“…An alignment of the chicken and human IL-4Rα protein sequences identified the amino acid positions orthologous to sites 5 and 520 in chicken (Additional file 1 ). The site orthologous to the latter is segregating in humans (C431R, rs1805012) [ 67 , 68 ] at an intermediate frequency of over 10% in the population [ 69 ], similar to the chicken polymorphism. Substitution C431R is in the cytoplasmic domain of the receptor and is linked with better survival from gliomas in humans [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

Evidence of balanced diversity at the chicken interleukin 4 receptor alpha chain locus

et al. 2009

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BackgroundThe comparative analysis of genome sequences emerging for several avian species with the fully sequenced chicken genome enables the genome-wide investigation of selective processes in functionally important chicken genes. In particular, because of pathogenic challenges it is expected that genes involved in the chicken immune system are subject to particularly strong adaptive pressure. Signatures of selection detected by inter-species comparison may then be investigated at the population level in global chicken populations to highlight potentially relevant functional polymorphisms.ResultsComparative evolutionary analysis of chicken (Gallus gallus) and zebra finch (Taeniopygia guttata) genes identified interleukin 4 receptor alpha-chain (IL-4Rα), a key cytokine receptor as a candidate with a significant excess of substitutions at nonsynonymous sites, suggestive of adaptive evolution. Resequencing and detailed population genetic analysis of this gene in diverse village chickens from Asia and Africa, commercial broilers, and in outgroup species red jungle fowl (JF), grey JF, Ceylon JF, green JF, grey francolin and bamboo partridge, suggested elevated and balanced diversity across all populations at this gene, acting to preserve different high-frequency alleles at two nonsynonymous sites.ConclusionHaplotype networks indicate that red JF is the primary contributor of diversity at chicken IL-4Rα: the signature of variation observed here may be due to the effects of domestication, admixture and introgression, which produce high diversity. However, this gene is a key cytokine-binding receptor in the immune system, so balancing selection related to the host response to pathogens cannot be excluded.

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Identification of a novel single‐nucleotide polymorphism (Val554Ile) and definition of eight common alleles for human IL4RA exon 11

Cited by 11 publications

References 15 publications

Interleukin-4 (IL4) and Interleukin-4 receptor (IL4RA) polymorphisms in asthma: a case control study

Interleukin-4 (IL4) and Interleukin-4 receptor (IL4RA) polymorphisms in asthma: a case control study

Epistatic effect of IL1A and IL4RA genes on the risk of atopy

Evidence of balanced diversity at the chicken interleukin 4 receptor alpha chain locus

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