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Macrophage Migration Inhibitory Factor Gene Polymorphism Is Associated with Sarcoidosis in Biopsy Proven Erythema Nodosum

MAHSA M. AMOLI, RACHELLE P. DONN, WENDY THOMSON, ALI H. HAJEER, CARLOS GARCIA-PORRUA, MERCEDES LUEIRO, WILLIAM E.R. OLLIER, and MIGUEL A. GONZALEZ-GAY

ABSTRACT.

Objective.
To assess whether polymorphism of the macrophage migration inhibitory factor (MIF) gene at the position -173 is implicated in the development of sarcoidosis.

Methods. Twenty-eight patients with biopsy proven erythema nodosum (EN) associated with sarcoidosis, 70 patients with biopsy proven EN related to other etiologies, and 122 healthy matched controls from the Lugo region of Northwest Spain were studied. Patients and controls were genotyped for a single nucleotide polymorphism in the 5'-flanking region at position -173 of the MIF gene, using SNapshot ddNTP primer extension, followed by capillary electrophoresis (ABI 3100).

Results. A significantly increased frequency of the C mutant allele was observed in patients with EN secondary to sarcoidosis compared to controls (p = 0.0016; pcorr = 0.0032; OR 2.78, 95% CI 1.45, 5.35) and also compared to patients with EN unrelated to sarcoidosis (p = 0.0004; pcorr = 0.0008; OR 3.72, 95% CI 1.75, 7.87). Patients with EN carrying an MIF 173 C allele were found to have an increased risk of sarcoidosis (57% in EN secondary to sarcoidosis vs 24% in patients with EN related to other etiologies; p = 0.002; p corr = 0.004; OR 4.16, 95% CI 1.64, 10.50).

Conclusion. This is the first attempt to assess the influence of MIF genetic polymorphism at position -173 in the development of sarcoidosis. The MIF 173 C allele is associated with a significantly increased risk of developing sarcoidosis in patients with EN. (J Rheumatol 2002;29:1671-73)

Key Indexing Terms:

SARCOIDOSIS
ERYTHEMA NODOSUM
MACROPHAGE MIGRATION INHIBITORY FACTOR GENE


From the ARC Epidemiology Unit, Manchester University Medical School, Manchester, United Kingdom; and the Divisions of Rheumatology and Dermatology, Hospital Xeral-Calde, Lugo, Spain.

M.M. Amoli, MD; R.P. Donn, MD, PhD; W. Thomson, PhD; A.H. Hajeer, PhD; W.E.R. Ollier, PhD, ARC Epidemiology Unit, Manchester University Medical School; M.A. Gonzalez-Gay, MD, PhD; C. Garcia-Porrua, MD, PhD, Rheumatology Division; M. Lueiro, MD, Dermatology Division, Hospital Xeral-Calde.

Address reprint requests to Dr. M.A. Gonzalez-Gay, Rheumatology Division, Hospital Xeral-Calde, c/ Dr. Ochoa s/n, 27004 Lugo, Spain. E-mail: miguelaggay@hotmail.com

Submitted November 9, 2001; revision accepted February 15, 2002.




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