Abstract
Background Transforming growth factor-β (TGF-β) may inhibit the development of atherosclerosis. We evaluated serum levels of TGF-β isoforms concurrently with serum levels of endotoxin and various inflammatory markers. In addition, we determined if any association exists between polymorphisms in the TGF-β1 gene and atherosclerosis in South African CKD patients. Methods We studied 120 CKD patients and 40 healthy controls. Serum TGF-β1, TGF-β2, TGF-β3, endotoxin, and inflammatory markers were measured. Functional polymorphisms in the TGF-β1 genes were genotyped using a polymerase chain reaction-sequence specific primer method and carotid intima media thickness (CIMT) was assessed by B-mode ultrasonography. Results TGF-β isoforms levels were significantly lower in the patients with atherosclerosis compared to patients without atherosclerosis (p<0.001). Overall, TGF-β isoforms had inverse relationships with CIMT. TGF-β1 and TGF-β2 levels were significantly lower in patients with carotid plaque compared to those without carotid plaque [TGF-β1: 31.9 (17.2 – 42.2) versus 45.9 (35.4 – 58.1) ng/ml, p=0.016; and TGF-β2: 1.46 (1.30 – 1.57) versus 1.70 (1.50 – 1.87) ng/ml, p=0.013]. In multiple logistic regression, age, TGF-β2, and TGF-β3 were the only independent predictors of subclinical atherosclerosis in CKD patients [age: odds ratio (OR), 1.054; 95% confidence interval (CI): 1.003 – 1.109, p=0.039; TGF-β2: OR, 0.996; 95% CI: 0.994–0.999, p=0.018; TGF-β3: OR, 0.992; 95% CI: 0.985–0.999, p=0.029). TGF-β1 genotypes did not influence serum levels of TGF-β1 and no association was found between the TGF-β1 gene polymorphisms and atherosclerosis risk. Conclusion TGF-β isoforms seem to offer protection against the development of atherosclerosis among South African CKD patients.
Highlights
Chronic kidney disease (CKD) patients are more likely to develop cardiovascular disease (CVD) than age-matched counterparts in the general population
This study has demonstrated that serum levels of TGFβ1, TGF-β2, and TGF-β3 are significantly reduced in CKD patients compared to the control group, especially in patients with subclinical atherosclerosis and carotid plaque
Our finding is in support of a previous study that showed that TGFβ1 expression inversely correlated with ankle-brachial index in patients with peripheral arterial disease [16]
Summary
Chronic kidney disease (CKD) patients are more likely to develop cardiovascular disease (CVD) than age-matched counterparts in the general population. It is reported that circulating endotoxaemia constitutes a strong risk factor for atherosclerotic CVD [8,9,10] This finding suggests that chronic exposure to endotoxins may be related to subclinical atherosclerosis and represents a reversible CVD risk factor in CKD patients. We determined if any association exists between polymorphisms in the TGF-β1 gene and atherosclerosis in South African CKD patients. TGF-β isoforms levels were significantly lower in the patients with atherosclerosis compared to patients without atherosclerosis (p
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