A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis
| Autor: | Padyukov, Leonid, Seielstad, Mark, Ong, Rick TH, Ding, Bo, Rönnelid, Johan, Seddighzadeh, Maria, Alfredsson, Lars, Klareskog, Lars, Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study group |
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| Rok vydání: | 2011 |
| Předmět: |
musculoskeletal diseases
Adult Cyclic Adolescent Arthritis Clinical Sciences Immunology Single Nucleotide Middle Aged Arthritis & Rheumatology Young Adult Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study group Gene Frequency Rheumatoid Case-Control Studies Public Health and Health Services Humans Genetic Predisposition to Disease Polymorphism Peptides Autoantibodies Aged Genome-Wide Association Study |
| Zdroj: | Annals of the rheumatic diseases, vol 70, iss 2 |
| Popis: | BackgroundRheumatoid arthritis (RA) can be divided into two major subsets based on the presence or absence of antibodies to citrullinated peptide antigens (ACPA). Until now, data from genome-wide association studies (GWAS) have only been published from ACPA-positive subsets of RA or from studies that have not separated the two subsets. The aim of the current study is to provide and compare GWAS data for both subsets.Methods and resultsGWAS using the Illumina 300K chip was performed for 774 ACPA-negative patients with RA, 1147 ACPA-positive patients with RA and 1079 controls from the Swedish population-based case-control study EIRA. Imputation was performed which allowed comparisons using 1,723,056 single nucleotide polymorphisms (SNPs). No SNP achieved genome-wide significance (2.9 × 10⁻⁸) in the comparison between ACPA-negative RA and controls. A case-case association study was then performed between ACPA-negative and ACPA-positive RA groups. The major difference in this analysis was in the HLA region where 768 HLA SNPs passed the threshold for genome-wide significance whereas additional contrasting SNPs did not reach genome-wide significance. However, one SNP close to the RPS12P4 locus in chromosome 2 reached a p value of 2 × 10⁶ and this locus can thus be considered as a tentative candidate locus for ACPA-negative RA.ConclusionsACPA-positive and ACPA-negative RA display significant risk allele frequency differences which are mainly confined to the HLA region. The data provide further support for distinct genetic aetiologies of RA subsets and emphasise the need to consider them separately in genetic as well as functional studies of this disease. |
| Databáze: | OpenAIRE |
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