ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1953

Identification of Genetic Factors Associated with Clinical Manifestations of Giant Cell Arteritis through a Stratified Large-Scale Analysis

Ana Márquez1, Francisco David Carmona2, Maria C. Cid3, José Hernández-Rodríguez3, Roser Solans4, Marc Ramentol4, Santos Castañeda5, Jose A. Miranda-Filloy6, Inmaculada C. Morado7, Javier Narváez8, Eugenio De Miguel9, Bernardo Sopeña10, Jordi Monfort11, Maria Jesus Garcia-Villanueva12, Norberto Ortego-Centeno13, Miguel Angel Gonzalez-Gay14, Javier Martín15 and Spanish GCA Group, 1Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, PTS-Granada and Systemic Autoimmune Diseases Unit, Hospital Clínico San Cecilio, Granada, Spain, 2Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, PTS-Granada, Granada, Spain, 3Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clínic University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, 4Autoimmune Systemic Diseases Unit, Department of Internal Medicine, Hospital Vall d’Hebron, Autonomous University of Barcelona, Barcelona, Spain, 5Department of Rheumatology, Hospital de la Princesa, IIS-Princesa, Madrid, Spain, 6Department of Rheumatology, Hospital Xeral-Calde, Lugo, Spain, 7Department of Rheumatology, Hospital Clínico San Carlos, Madrid, Spain, 8Rheumatology, Hospital Universitario de Bellvitge, Barcelona, Spain, 9Department of Rheumatology, Hospital Universitario La Paz, Madrid, Spain, 10Department of Internal Medicine, Complejo Hospitalario Universitario de Vigo, Vigo, Spain, 11Department of Rheumatology, Grup de recerca cel•lular en inflamació i cartílag. IMIM (Institut de Recerca Hospital del Mar), Barcelona, Spain, 12Department of Rheumatology, Hospital Ramón y Cajal, Madrid, Spain, 13Systemic Autoimmune Diseases Unit, Hospital Clínico San Cecilio, Granada, Spain, 14Rheumatology, Hospital Universitario Marqués de Valdecilla. IDIVAL, Santander, Spain, 15Instituto de Parasitología y Biomedicina López- Neyra, IPBLN-CSIC, PTS-Granada, Granada, Spain

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: ,

Session Information

Date: Monday, November 9, 2015

Title: Vasculitis Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Giant cell arteritis (GCA) is a large-vessel vasculitis that primarily affects the aorta and external carotid arteries and their branches, leading to ischemic manifestations such as headaches or jaw claudication. Visual loss, commonly secondary to anterior ischemic optic neuropathy, represents the most severe complication. Polymyalgia rheumatica (PMR), characterised by aching and morning stiffness in the neck, shoulder and pelvic girdle, is present in up to 50% of patients. Less often, neurological symptoms, such as transient ischemic attacks and strokes, have been identified in GCA patients. The aim of the present study was to perform a stratified analysis of a published Immunochip to identify genetic factors contributing to the main clinical manifestations of GCA.

Methods: Data from an Immunochip performed on 763 Spanish GCA patients were stratified according to the presence/absence of PMR, jaw claudication, visual manifestations (transient visual loss including amaurosis fugax, permanent visual loss, or diplopia) and stroke. Allele frequencies were compared between the different subgroups of GCA patients and 1,517 unaffected controls, and between patients with and without the considered phenotypes. Logistic regression analyses adjusted by the 3 first principal components and sex were performed using an additive model.

Results: After genotyping and quality control, 132,117 genetic variants were analyzed in GCA patients showing PMR (n=318), jaw claudication (n=331), visual manifestations (n=228) or stroke (n=43). Several loci showed suggestive associations with the different clinical manifestations, specifically MAFB (a transcription factor involved in the monocyte-macrophage differentiation) was associated with jaw claudication (p=2.31×10-6, OR=1.57), KIR2DL1/KIR2DL4 (transmembrane glycoproteins playing an important role in the immune response regulation) appeared to be involved in PMR (p=5.26×10-6, OR=1.69), ADAMTSL3 (implicated in angiogenesis and up regulated in astrocytes from the optic nerve in patients with glaucoma) showed an association with the development of visual manifestations (p=9.57×10-6, OR=1.69), and SULT6B1 (a sulfotransferase which catalyzes the sulfonation of xenobiotics, hormones and neurotransmitters) was implicated in GCA-associated stroke (p=1.67×10-5, OR=2.68). In all cases, the analysis of GCA patients accordingly with the presence/absence of each clinical condition also reached statistical significance (p=0.025, p=3.89×10-3, p=4.94×10-3 and p=8.96×10-6, respectively).

Conclusion: Using a stratified large-scale analysis, we have identified four novel loci potentially involved in the development of the main clinical complications occurring in GCA patients.

Disclosure: A. Márquez, None; F. D. Carmona, None; M. C. Cid, None; J. Hernández-Rodríguez, None; R. Solans, None; M. Ramentol, None; S. Castañeda, None; J. A. Miranda-Filloy, None; I. C. Morado, None; J. Narváez, None; E. De Miguel, None; B. Sopeña, None; J. Monfort, None; M. J. Garcia-Villanueva, None; N. Ortego-Centeno, None; M. A. Gonzalez-Gay, None; J. Martín, None.

To cite this abstract in AMA style:

Márquez A, Carmona FD, Cid MC, Hernández-Rodríguez J, Solans R, Ramentol M, Castañeda S, Miranda-Filloy JA, Morado IC, Narváez J, De Miguel E, Sopeña B, Monfort J, Garcia-Villanueva MJ, Ortego-Centeno N, Gonzalez-Gay MA, Martín J. Identification of Genetic Factors Associated with Clinical Manifestations of Giant Cell Arteritis through a Stratified Large-Scale Analysis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/identification-of-genetic-factors-associated-with-clinical-manifestations-of-giant-cell-arteritis-through-a-stratified-large-scale-analysis/. Accessed .

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