Rheumatology Advance Access published online on March 14, 2006
Rheumatology, doi:10.1093/rheumatology/kel058
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1 Instituto de Biomedicina, CSIC, Spain; These authors contributed equally to this work
* To whom correspondence should be addressed. 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 x 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.
Received September 12, 2005
Accepted January 27, 2006
Original Papers
No primary association of MICA polymorphism with systemic lupus erythematosus
E. Sánchez 1,
B. Torres 2,
J. R. Vilches 3,
M. A. López-Nevot 3,
N. Ortego-Centeno 4,
J. Jiménez-Alonso 5,
M. A. González-Gay 6,
E. de Ramón 7,
J. Sánchez-Román 8,
A. Núñez-Roldán 9,
J. Martín 1,
and
M. F. González-Escribano 2 *
2 Servicio de Inmunología, Hospital Virgen del Rocío, Spain; These authors contributed equally to this work
3 Servicio Inmunología, Hospital Virgen de las Nieves, Spain
4 Servicio de Medicina Interna, Hospital San Cecilio, Spain
5 Servicio de Medicina Interna, Hospital Virgen de las Nieves, Granada, Spain
6 Servicio de Reumatología, Hospital Xeral-Calde, Lugo, Spain
7 Servicio de Medicina Interna, Hospital Carlos-Haya, Malaga, Spain
8 Servicio de Medicina Interna, Hospital Virgen del Rocío, Sevilla, Spain
9 Servicio de Inmunología, Hospital Virgen del Rocío, Spain
M. F. González-Escribano, E-mail: mariaf.gonzalez.sspa{at}juntadeandalucia.es
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