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Open Access Highly Accessed Research article

The ZC3HC1 rs11556924 polymorphism is associated with increased carotid intima-media thickness in patients with rheumatoid arthritis

Raquel López-Mejías1, Fernanda Genre1, Mercedes García-Bermúdez2, Alfonso Corrales1, Carlos González-Juanatey3, Javier Llorca4, José A Miranda-Filloy5, Javier Rueda-Gotor1, Ricardo Blanco1, Santos Castañeda6, Javier Martín2 and Miguel A González-Gay1*

Author Affiliations

1 Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IFIMAV, Avenida de Valdecilla, s/n, Santander 39008, Spain

2 Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Granada, Spain

3 Cardiology Division, Hospital Lucus Augusti, Lugo, Spain

4 Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), IFIMAV, Santander, Spain

5 Division of Rheumatology, Hospital Lucus Augusti, Lugo, Spain

6 Rheumatology Department, Hospital Universitario la Princesa, IIS-Princesa, Madrid, Spain

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Arthritis Research & Therapy 2013, 15:R152  doi:10.1186/ar4335

Published: 11 October 2013

Abstract

Introduction

Rheumatoid arthritis (RA) is a complex polygenic disease associated with chronic inflammation, accelerated atherosclerosis and increased cardiovascular (CV) mortality. A recent meta-analysis has described the ZC3HC1 rs11556924 polymorphism as one of the most important signals associated with coronary artery disease (CAD) in non-rheumatic Caucasian individuals. In this study we evaluated the potential association of this gene polymorphism with subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in RA patients.

Methods

This study included 502 RA patients from Northern Spain. The ZC3HC1 rs11556924 polymorphism was genotyped with TaqMan single-nucleotide polymorphism (SNP) genotyping assays (C__31283062_10) in a 7900HT real-time polymerase chain reaction (PCR) system. cIMT was also assessed in these patients by carotid ultrasonography (US) technology.

Results

RA patients carrying the TT genotype had significantly higher cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.76 ± 0.18 mm and mean ± SD: 0.71 ± 0.16 mm respectively; P = 0.03) even after adjusting the results for sex, age at the time of US study, follow-up time and traditional CV risk factors (P = 0.04) evidencing that the effect conferred by ZC3HC1 rs11556924 polymorphism is independent of the traditional CV risk factors.

Conclusion

Our results indicate that ZC3HC1 rs11556924 polymorphism is associated with subclinical atherosclerosis in RA.