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Functional haplotypes of IL-12B are associated with childhood atopic asthma.

Authors: Hirota, T  Suzuki, Y  Hasegawa, K  Obara, K  Matsuda, A  Akahoshi, M  Nakashima, K  Cheng, L  Takahashi, N  Shimizu, M  Doi, S  Fujita, K  Enomoto, T  Ebisawa, M  Yoshihara, S  Nakamura, Y  Kishi, F  Shirakawa, T  Tamari, M 
Citation: Hirota T, etal., J Allergy Clin Immunol. 2005 Oct;116(4):789-95. Epub 2005 Aug 8.
Pubmed: (View Article at PubMed) PMID:16210052
DOI: Full-text: DOI:10.1016/j.jaci.2005.06.010

BACKGROUND: IL-12 is a heterodimeric proinflammatory cytokine that forms a link between innate and adaptive immunity. Although associations between polymorphisms of IL-12B on chromosome 5q31-33 and asthma have been reported, the genetic influences of the polymorphisms and haplotype of IL-12B are unclear. OBJECTIVE: To examine whether polymorphisms in IL-12B are associated with childhood atopic asthma in a Japanese population. METHODS: We identified a total of 13 polymorphisms and characterized the linkage disequilibrium mapping of the gene. Three variants in the promoter and 3' untranslated region were genotyped, and we conducted case-control and case-only association studies between those variants and asthma-related phenotypes (childhood atopic asthma, n = 297; normal controls, n = 555). Haplotype association analysis and functional analysis of these variants were also performed. RESULTS: 3' Untranslated region 10841C > A was significantly associated with the risk of childhood atopic asthma (P = .00062). The -6415 promoter variant, in linkage disequilibrium with the 10841C > A (D' = 0.78 and r2 = 0.61), was also marginally associated with childhood atopic asthma (P = .051). We analyzed the 2-locus haplotype by using these 2 polymorphisms and found a positive association with haplotype CTCTAA-C (-6415 CTCTAA and 10841C; P = .00078). Furthermore, 10841C > A affects the stability of transcripts, and promoter variant -6415GC enhances the transcriptional level of IL-12B. CONCLUSION: Our results imply that functional haplotype CTCTAA-C, which affects the instability of transcripts and the lower transcriptional level of IL-12B, has a protective effect in childhood atopic asthma. On the basis of these findings, the IL-12B gene might be involved in the development of atopic asthma through functional genetic polymorphisms.


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CRRD Object Information
CRRD ID: 4145438
Created: 2010-11-04
Species: All species
Last Modified: 2010-11-04
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.