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Published ahead of print on February 12, 2004, doi:10.1164/rccm.200307-933OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 9, May 2004, 1014-1018

A more recent version of this article appeared on May 1, 2004
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Submitted on July 16, 2003
Accepted on February 6, 2004

Functional Polymorphisms in the Promoter Region of Macrophage Migration Inhibitory Factor and Atopy

Nobuyuki Hizawa1*, Etsuro Yamaguchi2, Daisuke Takahashi1, Jun Nishihira3, and Masaharu Nishimura1

1 First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan, 2 Department of Respiratory and Allergy Medicine, Aichi Medical University, Aichi, Japan, 3 Department of Molecular Chemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan

* To whom correspondence should be addressed. E-mail: nhizawa{at}med.hokudai.ac.jp.

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; OR for homozygotes of -173C allele was 3.67 (compared to homozygotes of -173G allele, 95% CI=1.43-9.46, p<0.01), and OR for non-carriers of the -794 [5-CATT] allele was 3.51 (compared to 5-CATT repeat homozygotes, 95% CI=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 Japanese.
Key words: Candidate genes, Case-control association study, Specific IgE




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