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

G Vargas-Alarcón¹, J D Londoño², G Hernández-Pacheco¹, C Pacheco-Tena³, E Castillo¹, M H Cardiel², J Granados², R Burgos-Vargas³

¹ Department of Physiology, Instituto Nacional de Cardiología Ignacio Chávez, México DF, México
² Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México DF, México
³ Department of Rheumatology, Hospital General de México, México DF, México

Correspondence to:
Correspondence to:
Dr G Vargas-Alarcón, Department of Physiology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No 1, Tlalpan 14080, México DF, México;
gvargas63{at}yahoo.com

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 ² 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.

Keywords: genetics; HLA; Mexican population; spondyloarthropathies

Abbreviations: AF, aetiological fraction; AS, ankylosing spondylitis; BASDAI, Bath Ankylosing Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; MHC, major histocompatibility complex; OR, odds ratio; ReA, reactive arthritis; SpA, spondyloarthropathies

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