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

被引：42

作者：

Isidoro-García M. ^{[1
]}

Dávila I. ^{[2
]}

Laffond E. ^{[2
]}

Moreno E. ^{[2
]}

Lorente F. ^{[2
]}

González-Sarmiento R. ^{[1
]}

机构：

[1] Molecular Medicine Unit, Department of Medicine, University of Salamanca, Salamanca 37008, Campus Miguel de Unamuno

[2] Department of Allergy, University Hospital of Salamanca, Salamanca 37007

来源：

Clinical and Molecular Allergy | / 3卷 / 1期

关键词：

Asthma; Skin Prick Test; Allergic Asthma; Persistent Asthma; Asthma Phenotype;

D O I：

10.1186/1476-7961-3-15

中图分类号：

学科分类号：

摘要：

Background: IL4/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. Methods: A 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. Results: No 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]. Conclusions: Our 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. © 2005 Isidoro-Garcia et al., licensee BioMed Central Ltd.

引用

页数：20

共 40 条

[21]

Kruse S., Japha T., Tedner M., Sparholt S.H., Forster J., Kuehr J., Et al., The polymorphisms S503P and Q576R in the interleukin-4 receptor alpha gene are associated with atopy and influence the signal transduction, Immunology, 96, pp. 365-371, (1999)

[22]

Shirakawa I., Deichmann K.A., Izuhara I., Mao I., Adra C.N., Hopkin J.M., Atopy and asthma: Genetic variants of IL-4 and IL-13 signalling, Immunol Today, 21, pp. 60-64, (2000)

[23]

Sandford A.J., Chagani T., Zhu S., Weir T.D., Bai T.R., Spinelli J.J., Et al., Polymorphisms in the IL4, IL4RA, and FCERIB genes and asthma severity, J Allergy Clin Immunol, 106, pp. 135-140, (2000)

[24]

Kauppi P., Lindblad-Toh K., Sevon P., Toivonen H.T., Rioux J.D., Villapakkam A., Et al., A second-generation association study of the 5q31 cytokine gene cluster and the interleukin-4 receptor in asthma, Genomics, 77, pp. 35-42, (2001)

[25]

Wjst M., Kruse S., Illig T., Deichmann K., Asthma and IL-4 receptor alpha gene variants, Eur J Immunogenet, 29, pp. 263-268, (2002)

[26]

Bottini N., Borgiani P., Otsu A., Saccucci P., Stefanini L., Greco E., Et al., IL-4 receptor alpha chain genetic polymorphism and total IgE levels in the English population: Two-locus haplotypes are more informative than individual SNPs, Clin Genet, 61, pp. 288-292, (2002)

[27]

Cui T., Wang L., Wu J., Hu L., Xie J., Polymorphisms of IL-4, IL-4R alpha, and AICDA genes in adult allergic asthma, J Huazhong Univ Sci Technolog Med Sci, 23, pp. 134-137, (2003)

[28]

Isidoro-Garcia M., Davila I., Moreno E., Laffond E., Lorente F., Gonzalez-Sarmiento R., IL4RA gene polymorphism (Q576R) is associated with higher total IgE levels in Spanish patients with family history of atopy, Med Clin (Barc), 124, pp. 211-212, (2005)

[29]

Hytonen A.M., Lowhagen O., Arvidsson M., Balder B., Bjork A.L., Lindgren S., Et al., Haplotypes of the interleukin-4 receptor alpha chain gene associate with susceptibility to and severity of atopic asthma, Clin Exp Allergy, 34, pp. 1570-1575, (2004)

[30]

Lee S.G., Kim B.S., Kim J.H., Lee S.Y., Choi S.O., Shim J.Y., Et al., Gene-gene interaction between interleukin-4 and interleukin-4 receptor alpha in Korean children with asthma, Clin Exp Allergy, 34, pp. 1202-1208, (2004)

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