Association of Macrophage Migration Inhibitory Factor Polymorphisms with Total Plasma IgE Levels in Patients with Atopic Dermatitis in Korea.
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.
Departments of Dermatology, College of Medicine, The Catholic University of Korea, Uijongbu-City, Kyonggi-do, Korea.
Jung Soo
JS
Kim
Departments of Dermatology, College of Medicine, The Catholic University of Korea, Uijongbu-City, Kyonggi-do, Korea.
Jinyoung
J
Choi
Departments of Dermatology, College of Medicine, The Catholic University of Korea, Uijongbu-City, Kyonggi-do, Korea.
Hyung-Jin
HJ
Hahn
Departments of Dermatology, College of Medicine, The Catholic University of Korea, Uijongbu-City, Kyonggi-do, Korea.
Young-Bok
YB
Lee
Departments of Dermatology, College of Medicine, The Catholic University of Korea, Uijongbu-City, Kyonggi-do, Korea.
Dong-Soo
DS
Yu
Departments of Dermatology, College of Medicine, The Catholic University of Korea, Uijongbu-City, Kyonggi-do, Korea.
Jin-Wou
JW
Kim
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000235:genetics*; D019746:Intramolecular Oxidoreductases / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D008263:Macrophage Migration-Inhibitory Factors; D007073:Immunoglobulin E; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human