Abstract
The macrophage migration inhibitory factor (MIF) gene is located on human chromosome 22q11.2 and is linked to atopic phenotypes. Plasma MIF and log [total IgE] levels are significantly elevated in atopic dermatitis (AD) patients. The aim of this study was to evaluate the relationship between two MIF polymorphisms, −173 G to C and −794 CATT5–8, and total plasma IgE levels in AD patients in Korea. We performed PCR-RFLP analysis in 178 AD patients and 80 control subjects to determine whether MIF SNPs are associated with susceptibility to AD. Plasma total IgE and MIF levels were determined, and then logistic regression analyses were performed to determine the associations between a SNP or haplotype and plasma total IgE or MIF levels. The −173 G/C polymorphism, located in the MIF promoter, was significantly associated with AD; the odds ratios (ORs) for the CC homozygotes and GC heterozygotes were 9.3 and 2.5, respectively. The MIF C/5-CATT and the MIF C/7-CATT haplotypes were significantly associated with AD; the ORs for the MIF C/5-CATT and MIF C/7-CATT haplotypes were 9.7 and 4.5, respectively. Log [total IgE] levels were highly associated with the MIF −794 7-CATT polymorphism. Notably, the MIF C/7-CATT haplotype was associated with a decrease in plasma log [total IgE] levels in a gene dose-dependent manner. Although log [MIF] levels were not associated with the MIF polymorphisms, the frequencies of the MIF C/5-CATT haplotype-containing genotypes decreased in order of MIF levels. Our results demonstrate that MIF promoter polymorphisms in the −173 C allele and the MIF C/5-CATT and C/7-CATT haplotypes were significantly associated with an increased risk for AD. In particular, the −794 7-CATT locus and the MIF C/7-CATT haplotype were significantly associated with decreased total IgE levels in the plasma, suggesting that these polymorphisms might be a marker for intrinsic AD rather than extrinsic AD that shows high total IgE levels and presence of allergen-specific IgE.
Highlights
Atopic dermatitis (AD) is a multifactorial skin disease that appears to be affected by both genetic and environmental factors [1, 2]
About 60% of AD patients were positive for Dp-specific IgE, which was measured by a fluoro-enzyme immunoassay, and 61% of patients were Dermatophagoides farinae (Df) positive
We investigated the relationships between human migration inhibitory factor (MIF) promoter polymorphisms and plasma log [total IgE] levels in Korean AD patients
Summary
Atopic dermatitis (AD) is a multifactorial skin disease that appears to be affected by both genetic and environmental factors [1, 2]. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine [3], and serum MIF levels and regional skin lesions increase significantly in AD patients [4, 5]. The MIF −173 C allele confers an increased susceptibility to AD and higher MIF protein expression [10]. These polymorphisms in the MIF gene are associated with several immune-mediated inflammatory diseases, including atopy [12], asthma [13], juvenile idiopathic arthritis [9], rheumatoid arthritis[11], psoriasis [14, 15], and psoriatic arthritis [10, 16], suggesting that the polymorphisms are functionally important
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