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Abstract Number: 775

HLA-DRB1 Alleles in Susceptibility to Giant Cell Arteritis: Literature Review and Meta-Analysis

Sarah Mackie1, John Taylor1, Lubna Shafi2, Stephen Martin2, Bhaskar Dasgupta3, Andrew Gough4, Michael Green5, Lesley Hordon6, Stephen Jarrett7, Colin T. Pease8, Jennifer Barrett1, Richard Watts9,10 and Ann W. Morgan2, 1NIHR-Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Leeds, United Kingdom, 2Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom, 3Department of Rheumatology, Southend University Hospital, Essex, United Kingdom, 4Department of Rheumatology, Harrogate and District Foundation Trust, Harrogate, United Kingdom, 5Department of Rheumatology, York Teaching Hospital NHS Foundation Trust, York, United Kingdom, 6Department of Rheumatology, Mid Yorkshire Hospitals NHS Trust, Dewsbury, United Kingdom, 7Department of Rheumatology, Mid Yorkshire Hospitals NHS Trust, Wakefield, United Kingdom, 8Department of Rheumatology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, 9Rheumatology, Ipswich Hospitals NHS Trust, Ipswich, United Kingdom, 10Medicine, Norwich Medical School University of East Anglia, Norwich, United Kingdom

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: giant cell arteritis

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Session Information

Session Title: Vasculitis

Session Type: Abstract Submissions (ACR)

Background/Purpose

Giant cell arteritis (GCA) has been reported by many studies (but not all) to be associated with carriage of HLA-DRB1*04, with variable results relating to other alleles, but formal meta-analysis has never been performed. Our objective was to study the influence of HLA-DRB1 alleles on GCA susceptibility and incidence, combining new UK data with a meta-analysis of the literature.

Methods

GCA patients from the UK GCA Consortium were genotyped using single strand oligonucleotide polymerization, allele-specific polymerase chain reaction and direct sequencing. Control data was provided by the UK RA Genetics (UKRAG) Consortium. Meta-analysis was used to combine our results with previously-published data. Finally we determined the relationship of HLA-DRB1*04 population carrier frequency to the incidence of GCA reported in different countries.

Results

In the new UK data (225 cases, 1378 controls), HLA-DRB1*04 carriage was associated with GCA susceptibility (OR=2.69, p=1.5 x10-11), but HLA-DRB1*01 was protective (adjusted OR=0.55, p=0.0046). In meta-analysis combined with 14 published studies (an additional 691 cases, and 4038 controls), protective effects were seen from HLA-DR2, comprising HLA-DRB1*15 and HLA-DRB1*16 (OR=0.65, p=8.2×10-6), and possibly from HLA-DRB1*01 (OR=0.73, p=0.037). The incidence of GCA (n=17 countries) was associated with HLA-DRB1*04 allele frequency in the population (p=0.008; adjusted R2=0.51 on univariable analysis, adjusted R2=0.62 after also including latitude).

Conclusion

This meta-analysis confirms HLA-DRB1*04 as a GCA susceptibility allele but fails to show a susceptibility effect of HLA-DRB1*01, despite sharing amino acids in common in the third hypervariable region. Variations in population frequency of HLA-DRB1*04 might help explain worldwide variations in GCA incidence; latitude appears to make an independent contribution to GCA risk.


Disclosure:

S. Mackie,
None;

J. Taylor,
None;

L. Shafi,
None;

S. Martin,
None;

B. Dasgupta,

Novartis Pharma AG,

2;

A. Gough,
None;

M. Green,
None;

L. Hordon,

Menarini,

9,

UpToDate,

7;

S. Jarrett,

GlaxoSmithKline,

9;

C. T. Pease,
None;

J. Barrett,
None;

R. Watts,
None;

A. W. Morgan,
None.

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