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CCN2 (CTGF) gene polymorphism is a novel prognostic risk factor for cardiovascular outcomes in hemodialysis patients
Mario Cozzolino1, Maria Luisa Biondi, Elena Banfi
1Renal Division, S. Paolo Hospital, Milan, Italy.
Insights
The CCN2 gene polymorphism (G-945C) GG genotype is a significant predictor of cardiovascular mortality and events like stroke and heart attack in hemodialysis patients. This finding highlights a new risk factor for cardiovascular disease in this population.
Area of Science:
- Genetics
- Cardiovascular Medicine
- Nephrology
Background:
- Cardiovascular disease is a major cause of death in hemodialysis patients, linked to atherosclerosis.
- CCN2 (connective tissue growth factor) promotes fibrosis and is implicated in atherogenesis.
- Elevated CCN2 levels are found in atherosclerotic plaques, enhancing monocyte migration.
Purpose of the Study:
- To investigate the association between CCN2 gene polymorphism (G-945C) and cardiovascular morbidity and mortality in hemodialysis patients.
Main Methods:
- 98 hemodialysis patients were genotyped for the CCN2 G-945C polymorphism.
- Patients were followed for 24 months for cardiovascular events and mortality.
- Patient characteristics including age, comorbidities, and lifestyle factors were recorded.
Main Results:
- The GG genotype of the CCN2 G-945C polymorphism was strongly associated with increased cardiovascular mortality (OR 13, p=0.0048).
- The GG genotype was also significantly associated with major cardiovascular events, including stroke and myocardial infarction, in surviving patients (OR 13.3, p=0.0001).
- No association was found between CCN2 polymorphism and all-cause mortality.
Conclusions:
- CCN2 gene polymorphism is identified as a novel prognostic risk factor for cardiovascular morbidity and mortality in hemodialysis patients.
- These findings contribute to understanding the mechanisms linking accelerated atherosclerosis to higher mortality rates in hemodialysis populations.
Background:
The very high cardiovascular (CV) mortality and morbidity rates in hemodialysis (HD) patients are greatly related to atherosclerosis. CCN2 (connective tissue growth factor/CTGF) is a profibrotic factor that is secreted by endothelial cells, involved in atherogenesis, promoting fibroblast proliferation and matrix production. CCN2 protein is significantly increased in complicated fibrous plaques and enhances monocyte migration into atherosclerotic lesions. The aim of this study was to investigate a possible association between CCN2 gene polymorphism and CV morbidity and mortality in HD patients.
Methods:
98 HD patients, followed for 24 months, were genotyped for the common polymorphism on the CCN2 gene (G-945C). HD patient characteristics were: age 64 ± 13 years, males 64%, diabetes 24%, hypertension 62%, smokers 38%, dyslipidemia 28%, all undergoing standard HD three times weekly.
Results:
All-cause mortality was not associated with CCN2 polymorphism (G-945C). In contrast, however, the GG genotype was strongly associated with CV mortality: OR 13 (1.49-155), p = 0.0048. Interestingly, the GG genotype was also greatly associated with the serious CV events of stroke and myocardial infarction in surviving HD patients: OR 13.3 (2.5-87.08), p = 0.0001.
Conclusions:
We demonstrate for the first time that CCN2 gene polymorphism is a prognostic risk factor for CV morbidity and mortality in HD patients. These data may have important implications for better understanding the link between accelerated atherosclerosis and increased mortality in HD population.
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