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Asthma and genes encoding components of the vitamin D pathway

Bossé Yohan, Lemire Mathieu, Poon Audrey H, Daley Denise, He Jian-Qing, Sandford Andrew, White John H, James Alan L, Musk Arthur William, Palmer Lyle J, Benjamin Raby A, Weiss Scott T, Kozyrskyj Anita L, Becker Allan, Hudson Thomas J. et Laprise Catherine. (2009). Asthma and genes encoding components of the vitamin D pathway. Respiratory Research, 10, p. 98.

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Résumé

Background : Genetic variants at the vitamin D receptor (VDR) locus are associated with asthma and atopy. We hypothesized that polymorphisms in other genes of the vitamin D pathway are associated with asthma or atopy.

Methods : Eleven candidate genes were chosen for this study, five of which code for proteins in the vitamin D metabolism pathway (CYP27A1, CYP27B1, CYP2R1, CYP24A1, GC) and six that are known to be transcriptionally regulated by vitamin D (IL10, IL1RL1, CD28, CD86, IL8, SKIIP). For each gene, we selected a maximally informative set of common SNPs (tagSNPs) using the European-derived (CEU) HapMap dataset. A total of 87 SNPs were genotyped in a French-Canadian family sample ascertained through asthmatic probands (388 nuclear families, 1064 individuals) and evaluated using the Family Based Association Test (FBAT) program. We then sought to replicate the positive findings in four independent samples: two from Western Canada, one from Australia and one from the USA (CAMP).

Results : A number of SNPs in the IL10, CYP24A1, CYP2R1, IL1RL1 and CD86 genes were modestly associated with asthma and atopy (p < 0.05). Two-gene models testing for both main effects and the interaction were then performed using conditional logistic regression. Two-gene models implicating functional variants in the IL10 and VDR genes as well as in the IL10 and IL1RL1 genes were associated with asthma (p < 0.0002). In the replicate samples, SNPs in the IL10 and CYP24A1 genes were again modestly associated with asthma and atopy (p < 0.05). However, the SNPs or the orientation of the risk alleles were different between populations. A two-gene model involving IL10 and VDR was replicated in CAMP, but not in the other populations.

Conclusion : A number of genes involved in the vitamin D pathway demonstrate modest levels of association with asthma and atopy. Multilocus models testing genes in the same pathway are potentially more effective to evaluate the risk of asthma, but the effects are not uniform across populations.

Type de document:Article publié dans une revue avec comité d'évaluation
Volume:10
Pages:p. 98
Version évaluée par les pairs:Oui
Date:2009
Sujets:Sciences de la santé > Sciences médicales > Biologie cellulaire
Sciences de la santé > Sciences médicales > Biologie moléculaire
Sciences de la santé > Sciences médicales > Génétique
Département, module, service et unité de recherche:Départements et modules > Département des sciences fondamentales
Mots-clés:asthma, atopy, single nucleotide polymorphism, vitamin D, signal transduction, asthme, atopie, polymorphisme nucléotidique, vitamine D, transduction du signal
Informations complémentaires:This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Déposé le:28 août 2015 18:04
Dernière modification:05 déc. 2016 20:50
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