Rheumatology Advance Access originally published online on September 26, 2006
Rheumatology 2007 46(3):431-434; doi:10.1093/rheumatology/kel324
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Contribution of MHC class I region to genetic susceptibility for giant cell arteritis
Division of Rheumatology, Hospital Xeral-Calde, Lugo, 1Instituto de Parasitologia y Biomedicina Lopez-Neyra. CSIC, Granada, 2Division of Immunology, Hospital Virgen de las Nieves, Granada and 3Division of Immunology, Hospital Virgen del Rocio, Seville, Spain.
Correspondence to: Javier Martin MD, PhD, Instituto de Parasitología y Biomedicina, CSIC, Parque Tecnológico de Ciencias de la Salud. Avenida del Conocimiento s/n 18100-Armilla (Granada) Spain. E-mail: martin{at}ipb.csic.es
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Abstract |
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Objective. The aim of this study was to assess the potential contribution of HLA-class I MICA and HLA-B gene polymorphisms towards the pathogenesis of giant cell arteritis (GCA).
Methods. Ninety-eight biopsy-proven GCA patients and 225 ethnically matched controls from Lugo, Northwest Spain, were genotyped for the MICA–TM microsatellite polymorphism using a polymerase chain reaction (PCR)-based method. Genotyping of HLA-B was performed using PCR and detection with a reverse sequence-specific oligonucleotide (SSO) probes system.
Results. A significant difference in the distribution of the alleles of MICA between patient and control groups (P = 0.005) was found. This was due to an increased frequency of the MICA A5 allele in GCA patients compared with controls (26 vs 13.6%; P = 0.0001; PC = 0.0005; OR 2.2, 95% CI 1.4–3.4). In addition, the HLA-B*15 allele showed a higher frequency in GCA patients compared with controls (P = 0.004; PC = 0.04; OR 2.7, 95% CI 1.3–5.7). Interestingly, the association observed with the MICA A5 allele seems to be independent of linkage disequilibrium with HLA-B, as well as independent of that previously described with HLA-DRB1*04. Remarkably, simultaneous presence of MICA A5 and HLA-B*15 or HLA-DRB1*04 genetic markers leads to an increase in the OR obtained for each individual genetic marker (MICA A5 + B*15 OR 3.2; MICA A5 + DRB1*04 OR 5.8).
Conclusions. Our results provide the first evidence that the MICA and HLA-B genes are independently associated with the genetic susceptibility to GCA, and suggest that several genes within the MHC might have independent effects in the susceptibility to this systemic vasculitis.
KEY WORDS: Giant cell (temporal) arteritis, Genetics, MICA, HLA-B, HLA-DRB1, Susceptibility
The authors M. A. Gonzalez-Gay and J. Martin share senior authorship in this study.
Submitted 6 July 2006;
revised version accepted 22 August 2006.
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