Abstract 2181: A Genome-Wide SNP Chip Analysis Revealed Genes Regulating the Severity of Rheumatoid Arthritis (RA)
Authors
T. Matsubara, K. Funahashi, S. Toriyama, M. Muramatsu, M. Emi, S. Koyano
Purpose
To use genome-wide association analysis using high throughput single nucleotide polymorphism (SNP) typing technology to identify genes associated with severity of RA.
Methods
136 patients with varying degrees of RA disease activity were studied prior to treatment. Genome-wide SNP genotyping was performed by Illumina HumanHap300K chip technology. After evaluations of genotyping success rate > 90% and minor allele frequency > 1%, 285,548 SNPs were eligible for the study, out of a total of 316,994 SNPs. Regression analysis was employed to model association of 285,548 SNPs with DAS activity.
Results:
Five genes were strongly associated with DAS28 scores (using ESR or CRP for the DAS calculation). The five genes resided in pathways of intracellular transport, gene transcription and metabolism and included thryglobulin, lanosterol synthetase, catenin, Drosophila associated homolog, and vaculolar protein 54 sorting homolog. Some of these genes were also associated with response to biologics and radiological damage.
Conclusion:
The genes identified in this study may be involved in regulating the severity of RA. Further biological studies are warranted to investigate the mechanism by which these genes may be involved in the pathogenesis of RA.
Editorial Comment:
We will be seeing more and more studies using genome wide analysis to identify genes associated with the onset and severity of RA, as well as response to various RA treatments (two were recently published in New England Journal of Medicine). One of the powerful advantages of this technique is that it enables the identification of associated genes that might never have been considered based on biological plausibility alone. For example, what relationship might Drosophila associated homolog have, if any, to the pathogenesis of RA? These investigators were soundly criticized, however, by members of the audience for such preliminary results, as firm conclusions about genetic associations with disease can rarely be made on such a small number of patients and without validation in other independent cohorts.
