Rheumatology Advance Access published online on November 2, 2004
Rheumatology, doi:10.1093/rheumatology/keh459
Rheumatology © British Society for Rheumatology 2004; all rights reserved
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Internal Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, Perugia, Italy; Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden
* To whom correspondence should be addressed. Methods. HLA-DRB1-DQA1-DQB1 genotyping, MICA exon 5 microsatellite genotyping and HLA-B8 genotyping were performed in 48 Italian SLE patients and in 158 healthy control subjects. Results. Of HLA class II haplotypes, only DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) was significantly more frequent among SLE patients than among healthy control subjects [odds ratio (OR) = 6.5, corrected P<0.0026]. HLA-B8 was detected in 31% SLE patients and 13% healthy control subjects (OR = 3.0, P = 0.005). The allele-wise comparison between patients and controls showed that both MICA5 (OR = 2.5, corrected P<0.0005) and MICA5.1 (OR = 2.4, corrected P<0.0005) were positively and MICA9 (OR = 0.2, corrected P<0.0005) was negatively associated with the disease. The MICA5/5.1 genotype was positively associated with SLE (OR = 28.9, corrected P<0.0015) also in subjects negative for DR3-DQ2 (OR>22.6, corrected P<0.011). The simultaneous presence of DR3-DQ2 and MICA5.1 was detected in 15/48 (31%) SLE and in 10/158 (6%) healthy control subjects (OR = 6.7, corrected P<0.011). The simultaneous combination of DR3-DQ2 and MICA5 was found in 10/48 (21%) SLE patients and in only 1/158 healthy control subjects (OR = 41.3, corrected P<0.011). Logistic regression analysis showed the independent positive associations of MICA5 and MICA5.1 and negative association of MICA9 with the disease, and revealed that the interaction of the three major markers (DR3-DQ2, MICA5 and MICA5.1) was associated with increasing genetic risk, which was highest (OR>30.3) in DR3-DQ2-positive subjects carrying the MICA5-5.1 genotype. Conclusions. Our study provides the first demonstration of the independent association of the MICA gene polymorphism with genetic risk of SLE.
Accepted September 30, 2004
Original Papers
Contribution of MHC class I chain-related A (MICA) gene polymorphism to genetic susceptibility for systemic lupus erythematosus
2 Center for the Study of Rheumatic Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
3 Division of Medicine, Todi Hospital, Todi, Italy
4 Division of Biomedicine, Institution for Healthcare Sciences, Örebro University, Örebro, Sweden
5 Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden
6 Department of Gynaecology, Obstetrics and Paediatric Sciences, University of Perugia, Perugia, Italy
7 Department of Internal Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, Perugia, Italy
A. Falorni, E-mail: falorni{at}dimisem.med.unipg.it
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. A. Gonzalez-Gay, B. Rueda, J. R. Vilchez, M. A. Lopez-Nevot, G. Robledo, M. P. Ruiz, O. Fernandez, C. Garcia-Porrua, M. F. Gonzalez-Escribano, and J. Martin Contribution of MHC class I region to genetic susceptibility for giant cell arteritis Rheumatology, March 1, 2007; 46(3): 431 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Sanchez, B. Torres, J. R. Vilches, M. A. Lopez-Nevot, N. Ortego-Centeno, J. Jimenez-Alonso, M. A. Gonzalez-Gay, E. de Ramon, J. Sanchez-Roman, A. Nunez-Roldan, et al. No primary association of MICA polymorphism with systemic lupus erythematosus Rheumatology, September 1, 2006; 45(9): 1096 - 1100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Smerdel-Ramoya, C. Finholt, V. Lilleby, I.-M. Gilboe, H. F. Harbo, S. Maslinski, O. Forre, E. Thorsby, and B. A. Lie Systemic lupus erythematosus and the extended major histocompatibility complex--evidence for several predisposing loci Rheumatology, November 1, 2005; 44(11): 1368 - 1373. [Abstract] [Full Text] [PDF]
|
|