No primary association of MICA polymorphism with systemic lupus erythematosus

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-MICA5.1-88 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.