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Functional polymorphisms in the promoter region of macrophage migration inhibitory factor and atopy.

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Title: Functional polymorphisms in the promoter region of macrophage migration inhibitory factor and atopy.
Authors: Hizawa, Nobuyuki Browse this author
Yamaguchi, Elsuro Browse this author
Takahashi, Daisuke Browse this author
Nishihira, Jun Browse this author
Nishimura, Masaharu Browse this author →KAKEN DB
Keywords: candidate gene
case–control analysis
specific IgE
Issue Date: 1-May-2004
Publisher: American Thoracic Society (ATS)
Journal Title: American Journal of Respiratory and Critical Care Medicine
Volume: 169
Issue: 9
Start Page: 1014
End Page: 1018
Publisher DOI: 10.1164/rccm.200307-933OC
PMID: 14962818
Abstract: Macrophage migration inhibitory factor (MIF) is a pleiotrophic lymphocyte and macrophage cytokine; it is likely to play an important role in innate immunity. Genome-wide search for atopy susceptibility genes recently identified human chromosome 22q11, where the gene encoding MIF resides, as a region of interest for atopic traits. Both the –173G/C and –794 [CATT]5–8 repeat polymorphisms in the MIF promoter region are associated with altered levels of MIF gene transcription in vitro. We, therefore, hypothesized that these potentially functional polymorphisms may influence susceptibility to atopy and asthma. A case–control analysis examined the genetic influence of these promoter polymorphisms on the development of atopy and asthma in a Japanese population (n = 584). Evidence for significant association between the –173G/C and –794 [CATT]5–8 repeat polymorphisms and atopy was found; odds ratio for homozygotes of –173C allele was 3.67 (compared with homozygotes of –173G allele, 95% confidence interval = 1.43–9.46, p < 0.01), and odds ratio for noncarriers of the –794 [5-CATT] allele was 3.51 (compared with 5-CATT repeat homozygotes, 95% confidence interval = 1.82–6.78, p < 0.0005). No associations with asthma were detected. These results indicate that promoter polymorphisms in the MIF promoter region are risk factors for atopy and implicate MIF in the pathogenesis of atopy in a Japanese population. Macrophage migration inhibitory factor (MIF) is a pleiotrophic lymphocyte and macrophage cytokine; it is likely to play an important role in innate immunity. Genome-wide search for atopy susceptibility genes recently identified human chromosome 22q11, where the gene encoding MIF resides, as a region of interest for atopic traits. Both the –173G/C and –794 [CATT]5–8 repeat polymorphisms in the MIF promoter region are associated with altered levels of MIF gene transcription in vitro. We, therefore, hypothesized that these potentially functional polymorphisms may influence susceptibility to atopy and asthma. A case–control analysis examined the genetic influence of these promoter polymorphisms on the development of atopy and asthma in a Japanese population (n = 584). Evidence for significant association between the –173G/C and –794 [CATT]5–8 repeat polymorphisms and atopy was found; odds ratio for homozygotes of –173C allele was 3.67 (compared with homozygotes of –173G allele, 95% confidence interval = 1.43–9.46, p < 0.01), and odds ratio for noncarriers of the –794 [5-CATT] allele was 3.51 (compared with 5-CATT repeat homozygotes, 95% confidence interval = 1.82–6.78, p < 0.0005). No associations with asthma were detected. These results indicate that promoter polymorphisms in the MIF promoter region are risk factors for atopy and implicate MIF in the pathogenesis of atopy in a Japanese population.
Type: article
URI: http://hdl.handle.net/2115/17083
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 檜澤 伸之

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