ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 68

A Genome-Wide Association Study Identifies rs116199914 As an Intergenic Variant Associated with Carotid Intima-Media Thickness in Spanish Patients with Rheumatoid Arthritis

Raquel Lopez-Mejías1, Fernanda Genre1, Sara Remuzgo-Martínez1, David Carmona2,3, Verónica Pulito-Cueto1, Carlos González-Juanatey4, Alfonso Corrales1, Esther Vicente5, Jose A. Miranda-Filloy6, Beatriz-Segura Tejera7, Marco A. Ramírez Huaranga8, Verónica Mijares1, Leticia Lera-Gomez1, Ricardo Blanco1, Montserrat Robustillo-Villarino9, Javier Rodríguez-Carrio10, Ana Suárez10, Mercedes Alperi-López11, Francisco Javier Ballina-García12, Francisco Javier López Longo13, Francisco Javier Narváez14, Juan José Alegre9, Antonio Mera15, Eva Perez Pampín16, Antonio Gonzalez17, Enrique Raya Álvarez18, Chary López-Pedrera19, Carmen Gomez Vaquero14, Alejandro Balsa20, Dora Pascual-Salcedo20, Patricia Carreira21, Isidoro Gonzalez-Alvaro5, Luis Rodriguez Rodriguez22, Benjamin Fernandez Gutierrez22, Ivan Ferraz-Amaro23, Santos Castañeda24, Javier Martin3, Javier Llorca25 and Miguel Angel González-Gay1,26,27, 1Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, Spain, Santander, Spain, 2Departamento de Genética e Instituto de Biotecnología, Universidad de Granada, Granada, Spain, 3Instituto de Parasitología y Biomedicina ‘López-Neyra’, CSIC, PTS Granada, Granada, Spain, 4Division of Cardiology, Hospital Universitario Lucus Augusti, Lugo, Spain, 5Rheumatology Department, Hospital Universitario de La Princesa, IIS-IP, Madrid, Spain, 6Rheumatology Department, Hospital Universitario Lucus Augusti, Lugo, Spain, 7Rheumatology Division, Hospital Insular de Gran Canaria, Las Palmas, Spain, 8Rheumatology Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain, 9Rheumatology Department, Hospital Universitario Doctor Peset, Valencia, Spain, 10Area of Immunology, Department of Functional Biology, University of Oviedo, Oviedo, Spain, 11Department of Rheumatology, Hospital Universitario Central de Asturias, Asturias, Spain, 12Department of Rheumatology, Hospital Universitario Central de Asturias, Oviedo, Spain, 13Rheumatology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain, 14Rheumatology Department, Hospital Universitario de Bellvitge, Idibell, Barcelona, Spain, 15Rheumatology Division. Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain, 16Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain, 17Laboratorio Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain, 18Rheumatology, Hospital Universitario San Cecilio. Granada. Spain, Granada, Spain, 19IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain, 20Rheumatology Department, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain, 21Servicio de Reumatología, Hospital Universitario, Madrid, Spain, 22Rheumatology Department, Hospital Clínico San Carlos, Madrid, Spain, 23Rheumatology Division, Hospital Insular de Gran Canaria, La Laguna, Spain, 24Rheumatology, Rheumatology Department, Hospital Universitario de La Princesa, IIS-IP, Madrid, Spain, 25School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), Santander, Spain, 26School of Medicine, University of Cantabria, Santander, Spain, Santander, Spain, 27Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: , ,

Session Information

Date: Sunday, October 21, 2018

Title: Rheumatoid Arthritis – Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session A

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

Background/Purpose: Cardiovascular (CV) disease is the most common cause of morbidity and mortality in patients with rheumatoid arthritis (RA) [1, 2]. Traditional CV risk factors and chronic inflammation do not fully explain the increased CV predisposition observed in patients with RA [3]. In this regard, cumulative knowledge suggests that genetic factors may play a relevant role in this phenomenon [4]. To shed light onto the genetic background influencing the development of CV disease in patients with RA, we performed a genome-wide association study (GWAS) in a cohort of Spanish patients diagnosed with this condition.

Methods: After quality control filters, 2,989 Spanish patients with RA who fulfilled the 2010 American College of Rheumatology classification criteria [5] were analyzed. In addition, data on subclinical atherosclerosis, obtained by carotid ultrasonography (by assessment of carotid intima-media thickness-cIMT-and presence/absence of carotid plaques), was available for 1,355 of these patients.

Results: rs116199914 was identified as an intergenic variant associated with cIMT values at the genome-wide level of significance (minor allele (G): β=0.142, P=1.86E-08). In addition, suggestive signals of potential relevance were observed when both the presence/absence of CV events and subclinical atherosclerosis were evaluated, although none of them reached the genome-wide level of significance. Finally, a molecular pathway enrichment and a predictive protein-protein relationship analyses, including these suggestive GWAS signals, revealed a potential functional enrichment of the collagen biosynthesis network regarding the presence/absence of carotid plaques (GO:0032964, P=0.0497).

Conclusion: Our study suggests that the rs116199914 genetic variant is implicated in the increased CV risk observed in Spanish patients with RA.

[1] Arthritis Rheum 2007;57:125-32; [2] Best Pract Res Clin Rheumatol 2016;30:851-69; [3] Ann Rheum Dis 2018;77:48-54; [4] Autoimmun Rev 2016;15:1013-30; [5] Arthritis Rheum 2010;62:2569-81.

This study was supported by European Union FEDER funds and “Fondo de Investigación Sanitaria” (PI15/00525) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Program RD16/0012 (RIER) from ISCIII. RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, “Investing in your future”) (grant CP16/00033). FG is a recipient of a Sara Borrell post-doctoral fellowship from the ISCIII, co-funded by the ESF (grant CD15/00095). SR-M is supported by funds of the RETICS Program (RD16/0012/0009), co-funded by the European Regional Development Fund, ERDF. FDC was supported by the Ramón y Cajal programme of the Spanish Ministry of Economy and Competitiveness (RYC-2014-16458). VP-C is supported by funds of IDIVAL (PREVAL18/01). VM is supported by funds of a Miguel Servet type I programme (CP16/00033) (ISCIII, co-funded by ERDF).

Disclosure: R. Lopez-Mejías, None; F. Genre, None; S. Remuzgo-Martínez, None; D. Carmona, None; V. Pulito-Cueto, None; C. González-Juanatey, None; A. Corrales, None; E. Vicente, None; J. A. Miranda-Filloy, None; B. S. Tejera, None; M. A. Ramírez Huaranga, None; V. Mijares, None; L. Lera-Gomez, None; R. Blanco, None; M. Robustillo-Villarino, None; J. Rodríguez-Carrio, None; A. Suárez, None; M. Alperi-López, None; F. J. Ballina-García, None; F. J. López Longo, None; F. J. Narváez, None; J. J. Alegre, None; A. Mera, None; E. Perez Pampín, None; A. Gonzalez, None; E. Raya Álvarez, None; C. López-Pedrera, None; C. Gomez Vaquero, None; A. Balsa, None; D. Pascual-Salcedo, None; P. Carreira, None; I. Gonzalez-Alvaro, None; L. Rodriguez Rodriguez, None; B. Fernandez Gutierrez, None; I. Ferraz-Amaro, None; S. Castañeda, None; J. Martin, None; J. Llorca, None; M. A. González-Gay, None.

To cite this abstract in AMA style:

Lopez-Mejías R, Genre F, Remuzgo-Martínez S, Carmona D, Pulito-Cueto V, González-Juanatey C, Corrales A, Vicente E, Miranda-Filloy JA, Tejera BS, Ramírez Huaranga MA, Mijares V, Lera-Gomez L, Blanco R, Robustillo-Villarino M, Rodríguez-Carrio J, Suárez A, Alperi-López M, Ballina-García FJ, López Longo FJ, Narváez FJ, Alegre JJ, Mera A, Perez Pampín E, Gonzalez A, Raya Álvarez E, López-Pedrera C, Gomez Vaquero C, Balsa A, Pascual-Salcedo D, Carreira P, Gonzalez-Alvaro I, Rodriguez Rodriguez L, Fernandez Gutierrez B, Ferraz-Amaro I, Castañeda S, Martin J, Llorca J, González-Gay MA. A Genome-Wide Association Study Identifies rs116199914 As an Intergenic Variant Associated with Carotid Intima-Media Thickness in Spanish Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/a-genome-wide-association-study-identifies-rs116199914-as-an-intergenic-variant-associated-with-carotid-intima-media-thickness-in-spanish-patients-with-rheumatoid-arthritis/. Accessed .

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