HLA-C alleles confer risk for anti-citrullinated peptide antibody-positive rheumatoid arthritis independent of HLA-DRB1 alleles.
| Autor: | Nordang GB; Department of Medical Genetics, Oslo University Hospital, Postboks 4956 Nydalen, 0424 Oslo, Norway. b.a.lie@medisin.uio.no., Flåm ST, Maehlen MT, Kvien TK, Viken MK, Lie BA |
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| Jazyk: | angličtina |
| Zdroj: | Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2013 Nov; Vol. 52 (11), pp. 1973-82. Date of Electronic Publication: 2013 Jul 30. |
| DOI: | 10.1093/rheumatology/ket252 |
| Abstrakt: | Objective: The MHC exerts the greatest contribution to RA susceptibility, where certain HLA-DRB1 alleles confer the greatest risk. Interestingly, there is evidence for more risk factors in the MHC with regions surrounding the HLA class I loci, but whether these antigen-presenting loci could be causal risk variants has not been directly investigated. In this study we investigate the HLA association by direct genotyping of the HLA loci. Methods: Nine hundred and fifty RA patients and 933 healthy controls were genotyped for HLA-A, -B and -C. Eleven single-nucleotide polymorphisms (SNPs) and one insertion/deletion in the MHC were also included. Conditional logistic regression analyses were performed separately in ACPA-positive and -negative RA to identify the strongest susceptibility locus and additional risk loci. Results: In ACPA-positive RA, the most significantly associated locus was HLA-DRB1 (P = 1.58 × 10(-54)), with SE alleles being predisposing. After controlling for HLA-DRB1, the HLA-C locus was found to confer susceptibility (P = 2.32 × 10(-9)), particularly, the HLA-C*03 allele. Also, in ACPA-negative RA, HLA-DRB1 was the most significant locus (P = 7.22 × 10(-9)), but with other risk alleles (particularly DRB1*03). A possible independent involvement of HLA-C was also observed for ACPA-negative RA (P = 0.02). Conclusion: HLA-DRB1 was the major MHC risk locus in both ACPA-positive and ACPA-negative RA, but with allelic risk heterogeneity. Joint analyses of the HLA class I loci together with previously proposed SNP associations pointed at HLA-C as a second susceptibility locus in ACPA-positive RA. |
| Databáze: | MEDLINE |
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