ab222014

E-selectin polymorphism in erythema nodosum secondary to sarcoidosis

M.M. Amoli¹, J. Llorca², A. Gomez-Gigirey³, C. Garcia-Porrua³, M. Lueiro⁴, M. El-Magadmi¹, M.L. Fernandez⁴, W.E.R. Ollier¹, M.A. Gonzalez-Gay³

¹Centre for Integrated Genomic Medical Research, School of Epidemiology, and Health Sciences, University of Manchester, Manchester, United Kingdom; ²Division
of Preventive Medicine and Public Health, School of Medicine, University of Cantabria, Santander, Spain; and ³Division of Rheumatology and 4Division of Dermatology, Hospital Xeral-Calde, Lugo, Spain.

ABSTRACT
Objective
E-selectin is expressed on cytokine-stimulated endothelial cells and plays an important role in leukocyte-endothelium interactions and inflammatory cell recruitment. An A/C polymorphism at position +561 in the E-selectin gene, which yields an amino acid exchange from serine to arginine at position 128 in the epidermal growth factor-like domain, has been described. We have assessed whether this bi-allelic polymorphism may be implicated in the clinical expression of erythema nodosum (EN) secondary to sarcoidosis.

Methods
Thirty-one patients with biopsy-proven erythema nodosum (EN) associated with sarcoidosis, 68 patients with biopsy-proven EN related to other etiologies and 66 healthy matched controls from the Lugo region of Northwest Spain were studied. Patients and controls were genotyped for the A/ C polymorphism gene by PCR-restriction fragment length polymorphism.

Results
A significantly reduced frequency of the C mutant allele was observed in patients with EN secondary to sarcoidosis compared to controls (p = 0.019) and also compared to patients with EN unrelated to sarcoidosis (p = 0.028). This was also the case when the distribution of genotypes in patients with sarcoidosis was compared with that observed in patients with EN due to other etiologies (p = 0.028) and controls (p = 0.037). This was due to an absence in both C/A heterozygotes and C/C homozygotes in patients with EN secondary to sarcoidosis.

Conclusions
The present study constitutes the first attempt to assess the influence of E-selectin polymorphism at position +561 in the development of sarcoidosis. The C allele at the +561 position of the E-selectin gene is associated with significantly reduced risk of developing sarcoidosis in patients with EN.

Key words
Sarcoidosis, erythema nodosum, A561C E-selectin gene.

Please address correspondence to: Miguel A. Gonzalez-Gay, MD, PhD, Rheumatology Division. Hospital Xeral-Calde, c) Dr. Ochoa s/n, 27004 Lugo, Spain.
E-mail: miguelaggay@hotmail.com