Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Shah, Rachana; Matthews, Gregory J.; Shah, Rhia; McLaughlin, Charles W.; Chen, Jing; Wolman, M; Master, Stephen R.; Chai, Boyang; Xie, Dawei; Rader, Daniel J.; Raj, Dominic S.; Mehta, Nehal N.; Budoff, Matthew J.; Fischer, Michael J.; Go, Alan S.; Townsend, Raymond R.; He, Jiang; Kusek, John W.; Feldman, Harold I.; Foulkes, Andrea S.; Reilly, Muredach P.; Appel, Lawrence J.; Lash, James P.; Ojo, Akinlolu; Rahman, Mahboob

doi:10.1053/j.ajkd.2015.01.021

Cited by 47 publications

(32 citation statements)

References 35 publications

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“…38,40,46 Multiple small studies have examined the association of obesity with the CX3CR1 variants V249I and T280M, demonstrating an association with increased waist circumference, higher levels of HOMA-IR, and a trend towards association with type II DM and metabolic syndrome. 46,47 Despite these prior trends, we did not find any association between common variation in CCR2 , CCR5 or CX3CR1 and any glucometabolic traits in the large GIANT, DIAGRAM, MAGIC, and GLGC GWAS resources.…”

Section: Discussioncontrasting

confidence: 70%

Common and Rare Genetic Variation in CCR2 , CCR5 , or CX3CR1 and Risk of Atherosclerotic Coronary Heart Disease and Glucometabolic Traits

Golbus

Stitziel²,

Zhao

et al. 2016

Circ Cardiovasc Genet

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Background The chemokine receptors CCR2, CCR5, and CX3CR1 coordinate monocyte trafficking in homeostatic and inflammatory states. Multiple small human genetic studies have variably linked single nucleotide polymorphisms (SNPs) in these genes to cardiometabolic disease. We interrogated genome-wide association, exome sequencing, and exome array genotyping studies to ascertain the relationship between variation in these genes and coronary artery disease (CAD), myocardial infarction (MI), and glucometabolic traits. Methods and Results We interrogated the CARDIoGRAMplusC4D (60,801 cases, 123,504 controls), the MIGen and CARDIoGRAM Exome consortia (42,335 cases, 78,240 controls), and ESP EOMI (4,703 cases, 5,090 controls) datasets to ascertain the relationship between common, low frequency, and rare variation in CCR2, CCR5, or CX3CR1 with CAD and MI. We did not identify any variant associated with CAD or MI. We then explored common and low frequency variation in South Asians through PROMIS (9,058 cases, 8,379 controls), identifying six variants associated with MI including CX3CR1 V249I. Finally, reanalysis of the European HapMap imputed DIAGRAM, GLGC, GIANT and MAGIC datasets revealed no association with glucometabolic traits though three SNPs in PROMIS were associated with type II diabetes mellitus (DM). Conclusions No chemokine receptor variant was associated with CAD, MI, or glucometabolic traits in large European ancestry cohorts. In a South Asian cohort, we identified SNP associations with MI and type II DM but these did not meet significance in cohorts of European ancestry. These findings suggest the need for larger studies in South Asians but exclude clinically meaningful associations with CAD and glucometabolic traits in Europeans.

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Section: Discussioncontrasting

confidence: 70%

Common and Rare Genetic Variation in CCR2 , CCR5 , or CX3CR1 and Risk of Atherosclerotic Coronary Heart Disease and Glucometabolic Traits

Golbus

Stitziel²,

Zhao

et al. 2016

Circ Cardiovasc Genet

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“…In line with our findings, upregulation of CX 3 CL1 and CX 3 CR1 has been associated with plaque rupture in patients with unstable angina pectoris. 36 More recently, in a large cohort of patients from the Chronic Renal Insufficiency Cohort (CRIC) study, Shah et al 15 have showed that circulating CX 3 CL1 levels may contribute to both atherosclerosis and diabetes. 15 To our knowledge, our study is the first report showing an association between circulating CX 3 CL1 levels in idiopathic DVT in humans and its potential involvement in subsequent CV events.…”

Section: Discussionmentioning

confidence: 99%

“…11 Among them, fractalkine (CX 3 CL1) is a unique member of the CX 3 C subfamily that exists both as a soluble form, inducing chemotaxis, and as a membrane-bound form on the surface of inflamed endothelium, promoting cell-cell adhesion; in both cases, this involves activation of its cognate receptor CX 3 CR1. 12 Interestingly, circulating CX 3 CL1 has been recently associated with both atherosclerosis 13,14 and diabetes; 15 however, its potential involvement in DVT is unknown.…”

Section: Introductionmentioning

confidence: 99%

CX3CR1/CX3CL1 Axis Mediates Platelet–Leukocyte Adhesion to Arterial Endothelium in Younger Patients with a History of Idiopathic Deep Vein Thrombosis

Furio¹,

García-Fuster²,

Redón³

et al. 2018

Thromb Haemost

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Mechanisms linking deep vein thrombosis (DVT) and subclinical atherosclerosis and risk of cardiovascular events are poorly understood. The aim of this study was to investigate the potential impact of CXCR1/CXCL1 axis in DVT-associated endothelial dysfunction. The study included 22 patients (age: 37.5 ± 8.2 years) with a history of idiopathic DVT and without known cardiovascular risk factors and 23 aged-matched control subjects (age: 34 ± 7.8 years). Flow cytometry was used to evaluate peripheral markers of platelet activation, leukocyte immunophenotypes and CXCR1/CXCL1 expression in both groups. A flow chamber assay was employed to measure leukocyte arrest under dynamic conditions. Platelet activation and the percentage of circulating CXCR1-expressing platelets, CXCR1-expressing platelet-bound monocytes and CD8 lymphocytes were higher in patients with DVT than in controls. Additionally, patients with DVT had increased plasma levels of CXCL1, soluble P-selectin and platelet factor 4/CXCL4. Interestingly, this correlated with enhanced platelet-leukocyte interaction and leukocyte adhesion to TNFα-stimulated arterial endothelial cells, which was partly dependent on endothelial CXCL1 upregulation and increased CXCR1 expression on platelets, monocytes and lymphocytes. In conclusion, increased CXCR1 expression on circulating platelets may constitute a prognostic marker for long-term adverse cardiovascular events in patients with DVT. Blockade of CXCL1/CXCR1 axis may represent a new therapeutic strategy for the prevention of cardiovascular comorbidities associated with DVT.

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“…Based on the BMI data of the Chinese population, the Working Group on Obesity of the International Life Science Institute China Office recommended a BMI of 24 kg/m 2 as the cut-off value for overweight and 28 kg/m 2 as the cut-off value for obesity for Chinese [48]. The C-STRIDE cohort and the ROUTE cohort (Japan) [2] had similar BMI, both lower than that in Western studies [3–5]. Although some reports have suggested higher BMI as an independent risk factor for advanced CKD and CVD [49], the link between BMI and CVD is not clear cut.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and risk factors for cardiovascular disease among chronic kidney disease patients: results from the Chinese cohort study of chronic kidney disease (C-STRIDE)

et al. 2017

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BackgroundAlthough a high incidence of cardiovascular disease (CVD) is observed among chronic kidney disease (CKD) patients in developed countries, limited information is available about CVD prevalence and risk factors in the Chinese CKD population. The Chinese Cohort of Chronic Kidney Disease (C-STRIDE) was established to investigate the prevalence and risk factors of CVD among Chinese CKD patients.MethodsParticipants with stage 1–4 CKD (18–74 years of age) were recruited at 39 clinical centers located in 28 cities from 22 provinces of China. At entry, the socio-demographic status, medical history, anthropometric measurements and lifestyle behaviors were documented, and blood and urine samples were collected. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI creatinine equation. CVD diagnosis was based on patient self-report and review of medical records by trained staff. A multivariable logistic regression model was used to estimate the association between risk factors and CVD.ResultsThree thousand four hundred fifty-nine Chinese patients with pre-stage 5 CKD were enrolled, and 3168 finished all required examinations and were included in the study. In total, 40.8% of the cohort was female, with a mean age of 48.21 ± 13.70 years. The prevalence of CVD was 9.8%, and in 69.1% of the CVD cases cerebrovascular disease was observed. Multivariable analysis showed that increasing age, lower eGFR, presence of hypertension, abdominal aorta calcification and diabetes were associated with comorbid CVD among CKD patients. The odds ratios and 95% confidence intervals for these risk factors were 3.78 (2.55–5.59) for age 45–64 years and 6.07 (3.89–9.47) for age ≥65 years compared with age <45 years; 2.07 (1.28–3.34) for CKD stage 3a, 1.66 (1.00–2.62) for stage 3b, and 2.74 (1.72–4.36) for stage 4 compared with stages 1 and 2; 2.57 (1.50–4.41) for hypertension, 1.82 (1.23–2.70) for abdominal aorta calcification, and 1.70 (1.30–2.23) for diabetes, respectively.ConclusionsWe reported the CVD prevalence among a CKD patient cohort and found age, hypertension, diabetes, abdominal aorta calcification and lower eGFR were independently associated with higher CVD prevalence. Prospective follow-up and longitudinal evaluations of CVD risk among CKD patients are warranted.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-017-0441-9) contains supplementary material, which is available to authorized users.

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Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Cited by 47 publications

References 35 publications

Common and Rare Genetic Variation in CCR2 , CCR5 , or CX3CR1 and Risk of Atherosclerotic Coronary Heart Disease and Glucometabolic Traits

Common and Rare Genetic Variation in CCR2 , CCR5 , or CX3CR1 and Risk of Atherosclerotic Coronary Heart Disease and Glucometabolic Traits

CX3CR1/CX3CL1 Axis Mediates Platelet–Leukocyte Adhesion to Arterial Endothelium in Younger Patients with a History of Idiopathic Deep Vein Thrombosis

Prevalence and risk factors for cardiovascular disease among chronic kidney disease patients: results from the Chinese cohort study of chronic kidney disease (C-STRIDE)

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