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Abstract Number: 1205

Study of Association of CD40-CD154 Gene Polymorphisms with Disease Susceptibility and Cardiovascular Risk in Spanish Rheumatoid Arthritis Patients

Mercedes García-Bermúdez1, Carlos González-Juanatey2, Alfonso Corrales3, Raquel López-Mejías4, Maria Teruel5, Jose A. Miranda-Filloy6, Santos Castañeda-Sanz7, Alejandro Balsa8, B. Fernández-Gutierrez9, Isidoro González-Álvaro10, Carmen Gómez-Vaquero11, R. Blanco Alonso12, Javier Llorca13, Javier Martin14 and Miguel Angel González-Gay4, 1Immunology and Cellular Biology, Instituto de Parasitologia y Biomedicina López-Neyra, IPBLN-CSIC, Granada, Spain, 2Cardiology Division, Hospital Lucus Augusti, Lugo, Spain, 3Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Spain, Santander, Spain, 4Rheumatology, Hospital Universitario Marqués de Valdecilla. IFIMAV, Santander, Spain, 5Immunology, Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Granada, Spain, 6Rheumatology, Division of Rheumatology, Hospital Lucus Augusti, Lugo, Spain, 7Rheumatology, Hospital Universitario de La Princesa. Madrid. Spain, Madrid, Spain, 8Rheumatology, La Paz Hospital. IdiPaz, Madrid, Spain, 9Department of Rheumatology, Hospital Clinico San Carlos, Madrid, Spain, 10Servicio de Reumatología, Reumatología (Hospital Universitario de La Princesa), Madrid, Spain, 11Rheumatology Service, Hospital Universitari de Bellvitge - IDIBELL, Barcelona, Spain, 12Rheumatology, Hospital Universitario Marques de Valdecilla, Santander, Spain, 13Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), Santander, Spain, 14Immunology, Instituto de Parasitologia y Biomedicina Lopez-Neyra (IPBLN-CSIC), Granada, Spain

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Atherosclerosis, Cardiovascular disease and rheumatoid arthritis (RA)

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Session Information

Title: Rheumamtoid Arthritis - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) mortality. Since CD40-CD154 binding has direct consequences on inflammation process initiation, we aimed to replicate previous findings related to disease susceptibility in Spanish RA population. Furthermore, as the major complication in RA disease patients is the development of CV events due to accelerated atherosclerosis, and elevated levels of CD40L/CD154 are present in patients with acute myocardial infarction, we assessed the potential association of the CD40 (rs1883832, rs4810485 and rs1535045) and CD154/CD40L (rs3092952 and rs3092920) gene variants with CV risk in Spanish RA patients.

Methods: One thousand five hundred and seventy-five patients fulfilling the 1987 ACR classification criteria for RA and 1600 matched controls were genotyped for the CD40 rs1883832, rs4810485 and rs1535045 and CD154 rs3092952 and rs3092920 gene polymorphisms, using predesigned TaqMan single nucleotide polymorphism genotyping assays. Afterwards, we investigated the influence of CD40-CD154 gene variants in the development of CV events. Also, in a subgroup of 273 patients without history of CV events, we assessed the influence of these polymorphisms in the risk of subclinical atherosclerosis determined by carotid ultrasonography.

Results: Statistically significant differences in the allele frequencies for the rs1883832 CD40 gene promoter polymorphism between RA patients and controls were found.  Although we did not observe a significant association of CD40-CD154 gene variants with the development of CV events, an ANCOVA model adjusted for sex, age at the time of the ultrasonography assessment, follow-up time, traditional CV risk factors and anti-cyclic citrullinated peptide antibodies disclosed a significant association between CD40 rs1535045 polymorphism and carotid intima media thickness, a surrogate marker of atherosclerosis (p= 0.0047).

Conclusion: Our data indicate a potential association of rs1883832 CD40 gene polymorphism with susceptibility to RA. Also, the CD40 rs1535045 gene variant may influence development of subclinical atherosclerosis in RA patients.


Disclosure:

M. García-Bermúdez,
None;

C. González-Juanatey,
None;

A. Corrales,
None;

R. López-Mejías,
None;

M. Teruel,
None;

J. A. Miranda-Filloy,
None;

S. Castañeda-Sanz,
None;

A. Balsa,
None;

B. Fernández-Gutierrez,
None;

I. González-Álvaro,
None;

C. Gómez-Vaquero,
None;

R. Blanco Alonso,
None;

J. Llorca,
None;

J. Martin,
None;

M. A. González-Gay,
None.

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