Functional haplotypes of IL-12B are associated with childhood atopic asthma - 18/08/11
Reprint requests: Mayumi Tamari, MD, PhD, Laboratory for Genetics of Allergic Diseases, SNP Research Center, Institute of Physical and Chemical Research (RIKEN), 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045 Kanagawa, Japan.Kanagawa, Chiba, Kyoto, Osaka, Shiga, Wakayama, Tochigi, Tokyo, and Kagoshima, Japan
Abstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, IL-12B, polymorphism, association, linkage disequilibrium, haplotype
Abbreviations used : LD, OR, SNP, tIgE, UTR
Plan
| Supported by grants-in-aid from the Ministry of Health, Labor and Welfare; Japan Science and Technology Corp; and the Japanese Millennium project. |
Vol 116 - N° 4
P. 789-795 - octobre 2005 Retour au numéro
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