RESUMO
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.
Assuntos
Selectina E/genética , Eritema Nodoso/genética , Predisposição Genética para Doença , Polimorfismo de Fragmento de Restrição , Sarcoidose/genética , Adulto , Eritema Nodoso/complicações , Eritema Nodoso/patologia , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Sarcoidose/complicações , Sarcoidose/patologia , EspanhaAssuntos
Selectina E/genética , Predisposição Genética para Doença , Polimorfismo Genético , Vasculite/genética , Idoso , Vasos Sanguíneos/patologia , Criança , Feminino , Genótipo , Arterite de Células Gigantes/epidemiologia , Arterite de Células Gigantes/genética , Arterite de Células Gigantes/patologia , Humanos , Vasculite por IgA/epidemiologia , Vasculite por IgA/genética , Vasculite por IgA/patologia , Masculino , Pessoa de Meia-Idade , Espanha/epidemiologia , Vasculite/epidemiologia , Vasculite/patologia , Vasculite Leucocitoclástica Cutânea/epidemiologia , Vasculite Leucocitoclástica Cutânea/genética , Vasculite Leucocitoclástica Cutânea/patologia , População Branca/genéticaRESUMO
OBJECTIVE: E-selectin is expressed on cytokine stimulated endothelial cells and plays an important role in leukocyte-endothelium interactions and inflammatory cell recruitment. The gene for E-selectin is located at chromosome 1q 23-25 within the linkage area for systemic lupus erythematosus (SLE). The best characterized polymorphism in E-selectin molecule is A561C, which codes for Ser128Arg. We studied the prevalence of the A561C E-selectin gene polymorphism in patients with SLE and controls from 3 different ethnic populations. METHODS: Three cohorts of patients with SLE (1987 American College of Rheumatology criteria) and matching population controls were studied. These consisted of Caucasians of British Isles descent, Caucasians of Spanish origin, and Caucasians of Turkish origin. We used polymerase chain reaction and restriction fragment length polymorphism to genotype patients and controls. RESULTS: The numbers of patients and controls in each group were: UK (113 and 148), Spanish (145 and 179), and Turkish (93 and 96), respectively. The C allele occurred more frequently in UK and Spanish patients (OR 1.76, 95% CI 1.03-3.0, p = 0.037; and OR 1.84, 95% CI 1.1-3.09, p = 0.019), but not in Turkish patients (OR 1.03, 95% CI 0.55-1.97, p = 0.91). CONCLUSION: In 2 of 3 populations studied, the E-selectin C allele was significantly more common in SLE than in controls. E-selectin may be a susceptibility gene to SLE in these populations. Its role in disease expression and longterm outcomes such as accelerated atherosclerosis requires further study.