Associations of a novel IL4RA polymorphism, Ala57Thr, in Greenlander Inuit - 20/08/11
, Guicheng Zhang, PhD a, Vibeke Backer, MD, DMSci b, Celeste Porsbjerg, MD b, Steen Nepper-Christensen, MD b, Rhona Creegan, MSc c, Gareth Baynam, MBBS a, Nicholas de Klerk, PhD d, Giovanni A. Rossi, MD e, Isabel Hagel, PhD f, Maria C. Di Prisco, MD f, Neil Lynch, PhD f, John Britton, MD g, Ian Hall, MD g, Arthur W. Musk, MD, FRACP h, Jack Goldblatt, MD, FRACP c, Peter N. Le Souëf, MD, FRACP a, the Greenlandic Population Study Group 
Reprint requests: Siew-Kim Khoo, BSc (Hons), School of Paediatrics and Child Health, University of Western Australia, GPO Box D184, Perth, Australia 6001.Perth, Australia, Copenhagen, Denmark, Genoa, Italy, Caracas, Venezuela, and Nottingham, United Kingdom
Abstract |
Background |
A novel IL4RA polymorphism, Ala57Thr, was identified in Greenlander Inuit.
Objective |
We sought to determine whether the novel Thr57 allele is population specific and to assess the associations of Ala57Thr and Ile50Val with atopy in 2 Inuit populations.
Methods |
Ala57Thr and Ile50Val were genotyped in 651 Inuit living in Denmark, 1295 Inuit living in Greenland, and 1329 individuals from 7 populations from widely differing global locations. In Inuit the polymorphisms were evaluated for associations with atopy, rhinitis, asthma, and pulmonary function.
Results |
Thr57 was in linkage disequilibrium with Ile50 (D′ = 1, r2 = 0.13) and was common (33%) in the Inuit but rare (<0.6%) in all other populations. In Inuit living in Denmark, the Thr57 allele (in a dose-dependent manner) and the Ile50/Thr57 haplotype were associated with lower risk of atopy (Plinear = .003 and P = .034, respectively), with similar trends observed for atopic rhinitis and atopic asthma. In Inuit living in Greenland, Thr57 was not associated with atopy or atopic diseases, but Ile50 was weakly associated with lower risk of atopy.
Conclusion |
The novel IL4RA Ala57Thr was common in and population specific to Greenlander Inuit, with Thr57 associated with a lower risk of atopy in those living in Denmark. Hence a full investigation of genotype-phenotype relationships in a given population can only be achieved if each gene is screened for novel polymorphisms in that population.
Clinical implications |
Clinical risk attributable to variations in a gene in an ethnic group requires that all variations of the gene are known for that group.
Le texte complet de cet article est disponible en PDF.Key words : IL4RA polymorphism, atopy, asthma, rhinitis, Inuit
Abbreviations used : DRS, GM, OR, SNP
Plan
| S.-K. Khoo was supported by a National Health and Medical Research Council Grant. The Danish Lung Association, Asthma and Allergy Foundation, the Foundation of Wedell-Wedellsborg, and the Health Insurance Foundation supported the study, and GlaxoSK (Denmark) donated salbutamol (Ventoline), and ALK-Abelló, Hørsholm (Denmark) donated the allergen solutions. G. A. Rossi was funded by the Italian Ministry of Health. Disclosure of potential conflict of interest: G. A. Rossi has consultant arrangements with Abbott Laboratories, Altana, and Chiesi Farmaceutici and has received grant support from Abbott Laboratories, AstraZeneca, Byk Golden, Altana, Chiesi Farmaceutici, GlaxoSmithKline, Merck Sharpe and Dohme, and Schering Plough. The rest of the authors have declared that they have no conflict of interest. |
Vol 118 - N° 3
P. 627-634 - septembre 2006 Retour au numéro
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