Respiratory Research (Oct 2009)

Asthma and genes encoding components of the vitamin D pathway

  • Raby Benjamin A,
  • Palmer Lyle J,
  • Musk Arthur,
  • James Alan L,
  • White John H,
  • Sandford Andrew,
  • He Jian-Qing,
  • Daley Denise,
  • Poon Audrey H,
  • Lemire Mathieu,
  • Bossé Yohan,
  • Weiss Scott T,
  • Kozyrskyj Anita L,
  • Becker Allan,
  • Hudson Thomas J,
  • Laprise Catherine

DOI
https://doi.org/10.1186/1465-9921-10-98
Journal volume & issue
Vol. 10, no. 1
p. 98

Abstract

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Abstract 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 IL10 and VDR genes as well as in the IL10 and IL1RL1 genes were associated with asthma (p IL10 and CYP24A1 genes were again modestly associated with asthma and atopy (p 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.