Abstract
ObjectivesTo screen susceptibility loci for ankylosing spondylitis (AS) using an affected-only linkage analysis based on high-density single nucleotide polymorphisms (SNPs) in a genome-wide manner.Patients and MethodsAS patients from ten families with Cantonese origin of China were enrolled in the study. Blood samples were genotyped using genomic DNA derived from peripheral blood leukocytes by Illumina HumanHap 610-Quad SNP Chip. Genotype data were generated using the Illumina BeadStudio 3.2 software. PLINK package was used to remove non-autosomal SNPs and to further eliminate markers of typing errors. An affected-only linkage analysis was carried out using both non-parametric and parametric linkage analyses, as implemented in MERLIN.ResultSeventy-eight AS patients (48 males and 30 females, mean age: 39±16 years) were enrolled in the study. The mean age of onset was 23±10 years and mean duration of disease was 16.7±12.2 years. Iritis (2/76, 2.86%), dactylitis (5/78, 6.41%), hip joint involvement (9/78, 11.54%), peripheral arthritis (22/78, 28.21%), inflammatory back pain (IBP) (69/78, 88.46%) and HLA-B27 positivity (70/78, 89.74%) were observed in these patients. Using non-parameter linkage analysis, we found one susceptibility locus for AS, IBP and HLA-B27 in 6p21 respectively, spanning about 13.5Mb, 20.9Mb and 21.2Mb, respectively No significant results were found in the other clinical trait groups including dactylitis, hip involved and arthritis. The identical susceptibility locus region spanning above 9.44Mb was detected in AS IBP and HLA-B27 by the parametric linkage analysis.ConclusionOur genome-wide SNP linkage analysis in ten families with ankylosing spondylitis suggests a susceptibility locus on 6p21 in AS, which is a risk locus for IBP in AS patients.
Highlights
Ankylosing spondylitis (AS) is a subtype of spondyloarthritis (SpA), a group of inflammatory axial and peripheral joint diseases
Using non-parameter linkage analysis, we found one susceptibility locus for AS, inflammatory back pain (IBP) and HLA-B27 in 6p21 respectively, spanning about 13.5Mb, 20.9Mb and 21.2Mb, respectively No significant results were found in the other clinical trait groups including dactylitis, hip involved and arthritis
Linkage analysis with a high-density single nucleotide polymorphisms (SNPs) array was used for genome-wide scan in AS families, and a susceptibility locus on 6p21 was identified with nonparameter and parameter analysis, which is the first strong evidence supporting the linkage between MHC and AS by SNPs markers besides microsatellite markers
Summary
Ankylosing spondylitis (AS) is a subtype of spondyloarthritis (SpA), a group of inflammatory axial and peripheral joint diseases. The high concordance rate between monozygotic and dizygotic twins revealed that the heritability of AS exceeds 90% [3]. The recurrence risk for siblings has been reported to be as high as 82% [4]. In terms of genetic components, HLA-B27 is an important gene responsible for the familial aggregation of AS [5], with a concordance rate of 63% for monozygotic and 23% for dizygotic twin pairs [6]. HLA-B27 is considered to contribute about 20%-30% to the overall genetic risk for AS, while the whole MHC contributes approximately 40%-50% [3; 6], suggesting that other gene(s) might play an important role in the development of the disease
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