title: Asthma families show transmission disequilibrium of gene variants in the vitamin D metabolism and signalling pathway.
abstract: The vitamin D prophylaxis of rickets in pregnant women and newborns may play a role in early allergic sensitization. We now asked if an already diseased population may have inherited genetic variants in the vitamin D turnover or signalling pathway. Serum levels of calcidiol (25-OH-D3) and calcitriol (1,25-(OH)2-D3) were retrospectively assessed in 872 participants of the German Asthma Family Study. 96 DNA single base variants in 13 different genes were genotyped with MALDI-TOF and a bead array system. At least one positive SNP with a TDT of p < 0.05 for asthma or total IgE and calcidiol or calcitriol was seen in IL10, GC, IL12B, CYP2R1, IL4R, and CYP24A1. Consistent strong genotypic association could not be observed. Haplotype association were found only for CYP24A1, the main calcidiol degrading enzyme, where a frequent 5-point-haplotype was associated with asthma (p = 0.00063), total IgE (p = 0.0014), calcidiol (p = 0.0043) and calcitriol (p = 0.0046). Genetic analysis of biological pathways seem to be a promising approach where this may be a first entry point into effects of a polygenic inherited vitamin D sensitivity that may affect also other metabolic, immunological and cancerous diseases.
authors.affiliation: Institut für Epidemiologie, GSF--Forschungszentrum für Umwelt und Gesundheit, Ingolstädter Landstrasse 1, Neuherberg/Munich, Germany. wjst@gsf.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Wjst
authors.forename: Janine
authors.initials: J
authors.lastname: Altmüller
authors.forename: Theresia
authors.initials: T
authors.lastname: Faus-Kessler
authors.forename: Christine
authors.initials: C
authors.lastname: Braig
authors.forename: Margret
authors.initials: M
authors.lastname: Bahnweg
authors.forename: Elisabeth
authors.initials: E
authors.lastname: André
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D002112:Calcifediol / Q000097:blood; D002117:Calcitriol / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D004247:DNA / Q000032:analysis / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*; D013250:Steroid Hydroxylases / Q000235:genetics / Q000502:physiology; D014807:Vitamin D / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D014807:Vitamin D; D007073:Immunoglobulin E; D004247:DNA; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol; D002112:Calcifediol