Genetic markers of disease susceptibility and severity in giant cell arteritis and polymyalgia rheumatica

Semin Arthritis Rheum. 2003 Aug;33(1):38-48. doi: 10.1053/sarh.2002.50025.


Background and objectives: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common and often overlapping diseases that generally occur in elderly patients. In this article, we examine the role of different genes as markers of disease susceptibility and severity in GCA and PMR.

Methods: The influence of human leukocyte antigen (HLA)-DRB1 and tumor necrosis factor alleles, as well as the different allelic polymorphisms, on the susceptibility and severity to GCA and PMR was examined. A review of the literature was conducted.

Results: Most studies have described an association of GCA with HLA-DRB1(*)04 alleles. However, HLA-DRB1 association in patients with PMR varies from one population to another. In Northwest Spain, patients with GCA and PMR exhibited different tumor necrosis factor microsatellite polymorphism associations. Studies of intercellular adhesion molecule-1 biallelic polymorphisms have yielded contradictory results. Interleukin 1 cluster and tumor necrosis factor alpha polymorphisms increased susceptibility to GCA and PMR slightly. In Northwest Spain, interleukin 6 promoter polymorphism at position -174 modulated the phenotypic expression of PMR in biopsy-proven GCA. In the same population, regulated upon activation, normal T cell expressed and presumably secreted gene promoter biallelic polymorphism at position -403 was a marker for PMR susceptibility but not for GCA, and corticotropin-releasing hormone polymorphism appeared to be implicated in the risk of severe ischemic complications in patients with GCA.

Conclusions: The present analysis confirms that GCA and PMR are polygenic diseases. The search for additional genes is necessary to better understand the pathogenesis of these conditions.

Publication types

  • Review

MeSH terms

  • Animals
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Giant Cell Arteritis / genetics*
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Polymorphism, Genetic
  • Polymyalgia Rheumatica / genetics*
  • Tumor Necrosis Factor-alpha / genetics


  • Genetic Markers
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Tumor Necrosis Factor-alpha