Association of vitamin D receptor gene polymorphisms with childhood and adult asthma.
Vitamin D receptor (VDR) polymorphisms have been associated with several immune-related diseases, and VDR and vitamin D itself modulate T cell differentiation. VDR maps to chromosome 12q, near a region commonly linked to asthma. We evaluated VDR as part of a 12q positional candidate survey, and in response to observations of VDR polymorphism associations with asthma and atopy in a founder population of Quebec. Twenty-eight loci in 7 positional candidates (7 in VDR) were genotyped in 582 families. Whereas other candidates demonstrated no association, the VDR ApaI polymorphism demonstrated significant transmission distortion, with undertransmission of the C allele in a ratio of 4:5 (p = 0.01). This association was most prominent in girls, in whom distortion was more marked (p = 0.009). Sex-specific associations between multiple VDR polymorphisms and immunoglobulin E levels were also observed (p = 0.006-0.01). Asthma associations were replicated in a second cohort (517 females with asthma and 519 matched control subjects): 4 of 6 VDR variants demonstrated significant association (p = 0.02-0.04). The direction of association in this second cohort was opposite to the effects seen in the trios, but similar to findings in the Quebec study. These results suggest that VDR influences asthma and allergy susceptibility in a complex manner.
Channing Laboratory, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. benjamin.raby@channing.harvard.edu
Benjamin A
BA
Raby
Ross
R
Lazarus
Edwin K
EK
Silverman
Steven
S
Lake
Christoph
C
Lange
Mathias
M
Wjst
Scott T
ST
Weiss
D001249:Asthma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000453:epidemiology / Q000235:genetics*; D015994:Incidence; D008297:Male; D011110:Polymorphism, Genetic; D011336:Probability; D011792:Quebec / Q000453:epidemiology; D018167:Receptors, Calcitriol / Q000235:genetics*; D012016:Reference Values; D012720:Severity of Illness Index
D018167:Receptors, Calcitriol