Protective Effect of the IL33 rs3939286 Gene Polymorphism in the Development of Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis

Raquel López-Mejías¹, Fernanda Genre¹, Mercedes García-Bermúdez², Alfonso Corrales¹, Carlos González-Juanatey³, Begoña Ubilla¹, J. Llorca⁴, Encarnación Amigo⁵, Jose A. Miranda-Filloy⁶, Trinitario Pina Murcia¹, Ricardo Blanco⁷, Santos Castañeda⁸, Javier Martin⁹ and Miguel A González-Gay¹, ¹Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IDIVAL, Santander, Spain, ²Immunology and Cellular Biology, Instituto de Parasitologia y Biomedicina López-Neyra, IPBLN-CSIC, Granada, Spain, ³Hospital Universitario Lucus Augusti. Cardiology Division, Lugo, Spain, ⁴Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), IDIVAL, Santander, Spain, ⁵Hospital Universitario Lucus Augusti, Rheumatology Division, Lugo, Spain, ⁶Rheumatology, Division of Rheumatology, Hospital Lucus Augusti, Lugo, Spain, ⁷Hospital Marques de Valdecilla, Santander, Spain, ⁸Rheumatology, Hospital Universitario de La Princesa, IISP, Madrid, Spain, ⁹Immunology, Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Armilla (Granada), Spain

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Atherosclerosis, Cardiovascular disease, intima medial thickness, polymorphism and rheumatoid arthritis (RA)

Session Information

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Rheumatoid arthritis (RA) is a complex inflammatory disease characterized by chronic inflammation, accelerated atherosclerosis and increased cardiovascular (CV) mortality. Interleukin 33 (IL-33) is a cytokine with a pathogenic role in some autoimmune diseases and a potential protective effect on atherosclerosis. Recently, an association between the IL33 rs3939826 polymorphism and inflammatory bowel disease (a well-established chronic inflammatory disorder) has been described in Caucasian individuals. In the present study, we aimed to establish for first time whether this gene polymorphism influences the development of subclinical atherosclerosis in patients for RA.

Methods: 567 patients with RA from Northern Spain without a previous history of CV events were assessed by carotid ultrasonography (US) to determine the carotid intima-media wall thickness (cIMT). Also, the IL33 rs3939286 polymorphism was genotyped in these patients by TaqMan single-nucleotide polymorphism genotyping assays in a 7900 HT real-time polymerase chain reaction system.

Results: Patients with RA carrying the TT genotype had lower cIMT values than those homozygous for the CC genotype (mean ± standard deviation [SD]: 0.71 ± 0.14 mm in TT versus 0.76 ± 0.14 mm in CC carriers). Moreover, patients carrying the CT genotype had intermediate cIMT values (mean ± SD: 0.73 ± 0.17 mm). In keeping with these observations, patients with RA carrying the mutant allele T exhibited significantly lower cIMT values than those carrying the wild allele C (mean ± SD: 0.72 ± 0.16 mm versus 0.75 ± 0.18 mm, respectively; p=0.04). The association of allele T with lower values of cIMT in patients with RA remained statistically significant after adjusting the results for sex, age at the time of the carotid US study, follow-up time and traditional CV risk factors (p=0.02).

Conclusion: Our results indicate a protective effect of the IL33 rs3939286 gene polymorphism in the susceptibility to subclinical atherosclerosis in patients with RA.

This study was supported by European Union FEDER funds and “Fondo de Investigación Sanitaria” (grants PI06/0024, PS09/00748 and PI12/00060) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Programs RD12/0009 (RIER) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain), and in part by grants from the European IMI BTCure Program. RLM is a recipient of a Sara Borrell postdoctoral fellowship from the “Instituto Carlos III de Salud” at the Spanish Ministry of Health (Spain) (CD12/00425). FG and BU are supported by funds from the RETICS Program (RIER) (RD12/0009/0013).

Disclosure:

R. López-Mejías,
None;

F. Genre,
None;

M. García-Bermúdez,
None;

A. Corrales,
None;

C. González-Juanatey,
None;

B. Ubilla,
None;

J. Llorca,
None;

E. Amigo,
None;

J. A. Miranda-Filloy,
None;

T. Pina Murcia,
None;

R. Blanco,
None;

S. Castañeda,
None;

J. Martin,
None;

M. A. González-Gay,
None.

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