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No primary association of MICA polymorphism with systemic lupus erythematosus

2006; Oxford University Press; Volume: 45; Issue: 9 Linguagem: Inglês

10.1093/rheumatology/kel058

1462-0332

Elena Sánchez, Belén Torres, J. R. Vilches, Miguel Ángel López‐Nevot, Norberto Ortego‐Centeno, J Jiménez-Alonso, Miguel Á. González‐Gay, Enrique de Ramón, J Sánchez-Román, Antonio Núñez‐Roldán, Javier Martı́n, Marı́a-Francisca González-Escribano,

Systemic Lupus Erythematosus Research

Objective. To replicate the described association between MHC class I chain-related A (MICA) gene polymorphism and susceptibility to systemic lupus erythematosus (SLE). Methods. MICA transmembrane microsatellite polymorphism was genotyped using a polymerase chain reaction (PCR)-based method. Genotyping of HLA-B* and DRB1* was performed using PCR and detection with a reverse sequence-specific oligonucleotide (SSO) probe system. Combined data for these three loci (HLA-B*, DRB1* and MICA) were obtained from a total of 333 patients and 361 healthy controls. Results. Significant association with B*08 [P<10−7, odds ratio (OR) 3.17, 95% confidence interval (CI) 2.02–5.00], DRB1*0301 (P<10−7, OR 2.07, 95% CI 1.59–2.68) and MICA5.1 (P = 0.01, OR 1.23, 95% CI 1.04–1.46) was observed. The combinations DRB1*0301-MICA5.1-B8 and HLA-DRB1*0301-B*08-positive and MICA5-1-negative were more frequent among SLE patients (11.4 vs 3.3% in healthy controls, P = 3.9 × 10−5, OR 3.76, 95% CI 1.85–7.73, and 6.9 vs 1.7%, P = 0.0007, OR 4.32, 95% CI 1.68–13.10, respectively). Additionally, individuals who were HLA-DRB1*0301-B*08-negative and MICA5-1-positive were less frequent among patients (22.2 vs 31.3% in healthy controls, P = 0.007, OR 0.63, 95% CI 0.44–0.89) and the magnitude of the OR was similar to that obtained in individuals negative for all the three factors (OR 0.69, 95% CI 050–0.94). Further analysis performed to detect independent association strongly suggested that the association between MICA5.1 and SLE is secondary to the linkage disequilibrium of this allele with B*08. Conclusions. Our results do not support an independent association of MICA gene polymorphism with susceptibility to SLE.