E-selectin polymorphism in erythema nodosum secondary to sarcoidosis.
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.
Amoli
M M
MM
Centre for Integrated Genomic Medical Research, School of Epidemiology and Health Sciences, University of Manchester, Manchester, United Kingdom.
Llorca
J
J
Gomez-Gigirey
A
A
Garcia-Porrua
C
C
Lueiro
M
M
El-Magadmi
M
M
Fernandez
M L
ML
Ollier
W E R
WE
Gonzalez-Gay
M A
MA
D000328:Adult; D019040:E-Selectin / Q000235:genetics*; D004893:Erythema Nodosum / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012507:Sarcoidosis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D013030:Spain
D019040:E-Selectin