Effect of HLA-B and HLA-DR genes on susceptibility to and severity of spondyloarthropathies in Mexican patients

• Published in: Annals of the rheumatic diseases 2002-08, Vol.61 (8), p.714-717
• Main Authors: Vargas-Alarcón, G, Londoño, J D, Hernández-Pacheco, G, Pacheco-Tena, C, Castillo, E, Cardiel, M H, Granados, J, Burgos-Vargas, R
• Format: Article
• Language: English
• Subjects: Adult; aetiological fraction; Age of Onset; ankylosing spondylitis; BASDAI; BASFI; Bath Ankylosing Disease Activity Index; Bath Ankylosing Spondylitis Functional Index; Biological and medical sciences; Confidence intervals; Disease; Disease susceptibility; Diseases of the osteoarticular system; Extended Report; Female; Gene Frequency; Genes; Genetic aspects; Genetic Predisposition to Disease; genetics; Histocompatibility antigens; HLA; HLA histocompatibility antigens; HLA-B Antigens - genetics; HLA-B15 Antigen; HLA-B27 Antigen - genetics; HLA-DR1 Antigen - genetics; Humans; Inflammatory joint diseases; major histocompatibility complex; Male; Medical sciences; Mexican population; Mexicans; Mexico - ethnology; MHC; odds ratio; ReA; reactive arthritis; SpA; Spondylitis, Ankylosing - ethnology; Spondylitis, Ankylosing - genetics; Spondyloarthropathies; Studies
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.61.8.714

Objective: To investigate the role of HLA-B and HLA-DR genes as contributors to genetic susceptibility and clinical expression of the spondyloarthropathies (SpA) in the Mexican population. Methods: The study included 172 patients with SpA (undifferentiated SpA 83, ankylosing spondylitis (AS) 64, and reactive arthritis 25) and 99 healthy controls. The HLA-B and HLA-DR alleles were detected by the polymerase chain reaction with sequence-specific primers technique. Patient assessment included demographic data, diagnostic categories, and disease patterns. Statistical methods included the Mantel-Haenzel χ2 test, Fisher's exact test, and Woolf method for odds ratio (OR). Differences of continuous variables between HLA allele groups were calculated by Student's t test. Results: Increased frequencies of HLA-B27 (pCh10−3, OR=28.7), HLA-DR1 (pC=0.045, OR=2.77), and HLA-B15 (p=0.034, pC=NS, OR=2.04) alleles in the whole group were found. HLA-B27 strength of association (OR) was 41.4 in AS; 20.9 in undifferentiated SpA; 27.2 in reactive arthritis. HLA-DR1 and HLA-B15 were increased in undifferentiated SpA (pC=0.045, OR=2.98 and p=0.004, pC=NS, OR=2.75). By analysing 58 HLA-B27 negative patients it was found that HLA-B15 and HLA-DR1 associations with SpA were independent of HLA-B27; increased frequencies of HLA-B15 were found in the whole SpA group and in patients with undifferentiated SpA (pC=0.03, OR=3.09 and pCh0.01, OR=3.77) and of HLA-DR1 in the latter (p=0.04, pC=NS, OR=3.15). HLA-B27 positive patients were younger than HLA-B27 negative patients at onset (p=0.03), but HLA-DR1 positive patients were older than HLA-DR1 negative patients (p=0.03). Bath indices for disease activity and functioning were higher in HLA-B27 positive patients (p=0.006 and p=0.004 v HLA-B27 negative patients). In contrast, neither HLA-DR1 nor HLA-B15 influenced these indices. Conclusion: Apart from HLA-B27, there is a significant association of HLA-DR1 and HLA-B15 with SpA in Mexicans which is independent of B27. HLA-B27 is associated with younger age at onset and increased disease severity and HLA-DR1 with older age at onset. The strength of HLA-B15, HLA-B27, and HLA-DR1 associations varied in different forms of SpA.