Association of vitamin D receptor gene polymorphisms with childhood and adult asthma

被引:204
作者
Raby, BA [1 ]
Lazarus, R
Silverman, EK
Lake, S
Lange, C
Wjst, M
Weiss, ST
机构
[1] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Harvard Partners Ctr Genom & Genet, Boston, MA 02115 USA
[4] Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Boston, MA USA
[5] Harvard Univ, Sch Med, Cambridge, MA 02138 USA
[6] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA
[7] GSF, Natl Res Ctr Environm & Hlth, Inst Epidemiol, Neuherberg, Germany
关键词
association studies; asthma; genetics; replication; VDR;
D O I
10.1164/rccm.200404-447OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 Apa1 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.
引用
收藏
页码:1057 / 1065
页数:9
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