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

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.

SUBMITTER: Lopez-Mejias R

PROVIDER: S-EPMC3978706 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

López-Mejías Raquel R Genre Fernanda F García-Bermúdez Mercedes M Corrales Alfonso A González-Juanatey Carlos C Llorca Javier J Miranda-Filloy José A JA Rueda-Gotor Javier J Blanco Ricardo R Castañeda Santos S Martín Javier J González-Gay Miguel A MA

Arthritis research & therapy 20131011 5

<h4>Introduction</h4>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 asse ...[more]

PMID: 24286297

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Project description:The objective of this study was to assess the association of carotid intima-media thickness (CIMT), and also the presence of atheromatous plaque, with biological and targeted synthetic disease-modifying antirheumatic drugs, in an established cohort of patients with rheumatoid arthritis (RA). We conducted a cross-sectional observational study based on a cohort of patients with RA and a registry of healthy controls, in whom the CIMT and presence of atheromatous plaque were assessed by ultrasound. Data were collected on disease activity, lab results and treatments. Descriptive and bivariate analyses were performed and two multivariate linear regression models (with CIMT as the dependent variable) were constructed to identify variables independently associated with CIMT in our sample of patients with RA. A total of 176 individuals (146 patients with RA and 30 controls) were included. A higher percentage of patients than controls had atheromatous plaque (33.8% vs. 12.5%, p = 0.036), but no differences were found in terms of CIMT (0.64 vs. 0.61, p = 0.444). Compared to values in patients on other therapies, the CIMT was smaller among patients on tumour necrosis factor alpha (TNFα) inhibitors (mean [SD]: 0.58 [0.10] vs. 0.65 [0.19]; p = 0.013) and among those on Janus kinase inhibitors (mean [SD]: 0.52 [0.02] vs. 0.64 [0.18]; p < 0.001), while no differences were found as a function of the use of the other therapies considered. The multivariate linear regression analysis to identify factors associated with CIMT in our patients, adjusting for traditional cardiovascular risk factors such as hypertension, high levels of low-density lipoproteins, diabetes mellitus and smoking, showed that male sex, older age and having a greater cumulative erythrocyte sedimentation rate were independently associated with a larger CIMT, while patients on TNFα inhibitors had a CIMT 0.075 mm smaller than those on other treatments. The use of TNFα inhibitors may protect against subclinical atherosclerosis in patients with RA, patients on this biologic having smaller CIMTs than patients on other disease-modifying antirheumatic drugs. Nonetheless, these results should be confirmed in prospective studies with larger sample sizes.

Project description:BackgroundIntima-media thickness of the walls of the common carotid artery and internal carotid artery may add to the Framingham risk score for predicting cardiovascular events.MethodsWe measured the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery in 2965 members of the Framingham Offspring Study cohort. Cardiovascular-disease outcomes were evaluated for an average follow-up of 7.2 years. Multivariable Cox proportional-hazards models were generated for intima-media thickness and risk factors. We evaluated the reclassification of cardiovascular disease on the basis of the 8-year Framingham risk score category (low, intermediate, or high) after adding intima-media thickness values.ResultsA total of 296 participants had a cardiovascular event. The risk factors of the Framingham risk score predicted these events, with a C statistic of 0.748 (95% confidence interval [CI], 0.719 to 0.776). The adjusted hazard ratio for cardiovascular disease with a 1-SD increase in the mean intima-media thickness of the common carotid artery was 1.13 (95% CI, 1.02 to 1.24), with a nonsignificant change in the C statistic of 0.003 (95% CI, 0.000 to 0.007); the corresponding hazard ratio for the maximum intima-media thickness of the internal carotid artery was 1.21 (95% CI, 1.13 to 1.29), with a modest increase in the C statistic of 0.009 (95% CI, 0.003 to 0.016). The net reclassification index increased significantly after addition of intima-media thickness of the internal carotid artery (7.6%, P<0.001) but not intima-media thickness of the common carotid artery (0.0%, P=0.99). With the presence of plaque, defined as intima-media thickness of the internal carotid artery of more than 1.5 mm, the net reclassification index was 7.3% (P=0.01), with an increase in the C statistic of 0.014 (95% CI, 0.003 to 0.025).ConclusionsThe maximum internal and mean common carotid-artery intima-media thicknesses both predict cardiovascular outcomes, but only the maximum intima-media thickness of (and presence of plaque in) the internal carotid artery significantly (albeit modestly) improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort. (Funded by the National Heart, Lung, and Blood Institute.).

Dataset Information

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

Publications

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

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