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

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. 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. 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. 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.

González-Gay MA ，Amoli MM ，Garcia-Porrua C ，Ollier WE ... -  《SEMINARS IN ARTHRITIS AND RHEUMATISM》

Association of giant cell arteritis and polymyalgia rheumatica with different tumor necrosis factor microsatellite polymorphisms.

Mattey DL ，Hajeer AH ，Dababneh A ，Thomson W ，González-Gay MA ，García-Porrúa C ，Ollier WE ... -  《ARTHRITIS AND RHEUMATISM》

Distribution of HLA-DRB1 alleles of patients with polymyalgia rheumatica and giant cell arteritis in a Mediterranean population.

Combe B ，Sany J ，Le Quellec A ，Clot J ，Eliaou JF ... -  《JOURNAL OF RHEUMATOLOGY》

Intercellular adhesion molecule 1 gene polymorphisms in polymyalgia rheumatica/giant cell arteritis: association with disease risk and severity.

OBJECTIVE:Intercellular adhesion molecule 1 (ICAM-1) is widely distributed in shoulder synovial membrane of active polymyalgia rheumatica (PMR) and strongly expressed in granulomatous inflammatory infiltrate of the temporal artery in giant cell arteritis (GCA). ICAM-1 genes may contribute to the inflammatory PMR/GCA processes. We examined potential associations of ICAM-1 gene polymorphisms with PMR/GCA susceptibility and severity. METHODS:We enrolled 121 consecutive patients with "pure" PMR and 56 patients with biopsy positive GCA residing in Reggio Emilia, Italy. Among patients with PMR, 91 had a followup duration of at least one year. Selected as control subjects were 228 healthy blood donors, 75 patients with nonarteritic central retinal artery occlusion, and 116 cataract surgery patients from the same geographic area. All PMR/GCA patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphism at codon 241 (exon 4) and codon 469 (exon 6). RESULTS:The frequency of R241 was significantly higher in PMR/GCA patients [p = 0.00001, odds ratio (OR) 5.0 (95% confidence intervals, CI 2.6-9.6) ], in pure PMR patients [p = 0.00001, OR 5.0 (95% CI 2.5-10.0)], and in GCA patients [p = 0.00005; OR 5.0 (95% CI 2.2-11.5)] compared to the healthy controls. The frequency of R241 was significantly higher in total PMR/GCA patients compared to patients with nonarteritic central retinal artery occlusion [p = 0.0007; OR 5.3 (95% CI 1.8-15.5)] and cataract surgery patients [p = 0.0003; OR 4.1 (95% CI 1.8-9.0)]. The distribution of E/K 469 genotype was similar in PMR/GCA patients and in the 3 control groups. Cox proportional hazards modeling identified 2 variables that independently increased the risk of PMR relapse/recurrence: erythrocyte sedimentation rate at diagnosis > 72 mm/h [relative risk 1.6 (95% CI 1.1-2.3)] and the presence of R241 allele [relative risk 1.6 (95% CI 1.1-2.4)]. CONCLUSION:Our findings show that G/R 241 polymorphism of ICAM-1 is associated with PMR/GCA susceptibility and confers an increased risk of relapse/recurrence in PMR.

Salvarani C ，Casali B ，Boiardi L ，Ranzi A ，Macchioni P ，Nicoli D ，Farnetti E ，Brini M ，Portioli I ... -  《JOURNAL OF RHEUMATOLOGY》

Genetic epidemiology. Giant cell arteritis and polymyalgia rheumatica.

Gonzalez-Gay MA 《arthritis research》