PTPN22 R620W minor allele is a genetic risk factor for giant cell arteritis

Susan Lester; Alex W Hewitt; Carlee D Ruediger; Linda Bradbury; Elisabeth De Smit; Michael D Wiese; Rachel Black; Andrew Harrison; Graeme Jones; Geoffrey O Littlejohn; Tony R Merriman; Bain Shenstone; Malcolm D Smith; Maureen Rischmueller; Matthew A Brown; Catherine L Hill

doi:10.1136/rmdopen-2016-000246

PTPN22 R620W minor allele is a genetic risk factor for giant cell arteritis

RMD Open. 2016 Apr 7;2(1):e000246. doi: 10.1136/rmdopen-2016-000246. eCollection 2016.

Authors

Susan Lester¹, Alex W Hewitt², Carlee D Ruediger¹, Linda Bradbury³, Elisabeth De Smit⁴, Michael D Wiese⁵, Rachel Black⁶, Andrew Harrison⁷, Graeme Jones⁸, Geoffrey O Littlejohn⁹, Tony R Merriman¹⁰, Bain Shenstone¹¹, Malcolm D Smith¹², Maureen Rischmueller¹, Matthew A Brown³, Catherine L Hill¹³

Affiliations

¹ Department of Rheumatology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia; Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
² Genetics and Population Health , University of Western Australia , Perth, Western Australia , Australia.
³ Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Qld, Australia; University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Qld, Australia.
⁴ Centre for Eye Research , Melbourne, Victoria , Australia.
⁵ School of Pharmacy and Medical Sciences, University of South Australia , Australia.
⁶ Department of Rheumatology , The Queen Elizabeth Hospital , Woodville South, South Australia , Australia.
⁷ Department of Medicine , University of Otago Wellington , Wellington , New Zealand.
⁸ Department of Rheumatology , Menzies Research Institute, University of Tasmania , Hobart, Tasmania , Australia.
⁹ Department of Rheumatology , Monash Medical Centre , Clayton, Victoria , Australia.
¹⁰ Department of Biochemistry , University of Otago , Dunedin , New Zealand.
¹¹ Department of Rheumatology Concord Hospital, Concord, New South Wales , Australia.
¹² Department of Medicine , Flinders Medical Centre and Repatriation General Hospital , Adelaide, South Australia , Australia.
¹³ Department of Rheumatology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia; Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia; The Health Observatory, University of Adelaide, Adelaide, South Australia, Australia.

Abstract

Giant cell arteritis (GCA) is one of the commonest forms of vasculitis in the elderly, and may result in blindness and stroke. The pathogenesis of GCA is not understood, although environmental, infectious and genetic risk factors are implicated. One gene of interest is PTPN22, encoding lymphoid protein tyrosine phosphatase (Lyp), expressed exclusively in immune cells, which is proposed to be an 'archetypal non-HLA autoimmunity gene'. The minor allele of a functional PTPN22 single nucleotide polymorphism (rs2476601, R620W), which disrupts an interaction motif in the protein, was originally reported to be associated with biopsy-proven GCA in Spanish patients, with supporting data from three replicate Northern European studies. Recently, this observation was extended with additional patients and controls, and studies encompassing European, Scandinavian, UK and American patients. The aim of our study was to determine the association between PTPN22 rs2476601 (R620W) and biopsy-proven GCA in an Australian case cohort.

Keywords: Gene Polymorphism; Giant Cell Arteritis; Systemic vasculitis.