Genetic epidemiology of ankylosing spondylitis

Snelgrove, Tara (2006) Genetic epidemiology of ankylosing spondylitis. Masters thesis, Memorial University of Newfoundland.

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Abstract

Introduction: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis and represents the most common seronegative spondyloarthropathy with an approximate prevalence of one in one thousand Caucasians. Clinically, AS commonly presents as a predominantly axial arthritis affecting the spine and girdle joints. AS is a complex genetic disease with multiple susceptibility factors. Though it is known AS susceptibility has a strong genetic component, with a sibling recurrence risk (λs) of 82, the majority of the susceptibility genes are unidentified. -- Objective: The objective of this study was to identify and test potential candidate genes for susceptibility to AS in the Newfoundland population. Candidate genes were chosen based on functional relevance to disease phenotype or on positional proximity to known chromosome regions of linkage to AS. -- Methods: All patients with AS met the modified New York Criteria and the controls were ethnically matched. A Newfoundland cohort of 101 AS patients and 103 ethnically matched controls were genotyped using the Sequenom MassArray platform. All controls met Hardy Weinberg equilibrium. Analysis was performed using appropriate statistical tests. -- Results: The minor allele frequencies for the candidate genes TLR4 Asp299Gly (Pc=0.05) and TNFα promoter polymorphisms -308 (Pc=0.008), -863/-1031 (in linkage disequilibrium Pc=0.000) were found to be associated with AS. Other candidate genes tested showed no association with disease. Minor alleles of the single nucleotide polymorphisms chosen for the candidate genes FGFR2, TCIRG1, and DLL3 were not present in the Newfoundland population. No secondary associations of phenotype and genotype were noted for disease severity indices, gender or age of onset. -- Conclusion: A novel association was noted between TLR4 and AS and the association of promoter polymorphisms of TNFα was validated in the Newfoundland population.

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