Transforming Growth Factor-Beta Protects Against Inflammation-Related Atherosclerosis In South African Ckd Patients

Background. Transforming growth factor-beta (TGF-beta) may inhibit the development of atherosclerosis. We evaluated serum levels of TGF-beta isoforms concurrently with serum levels of endotoxin and various inflammatory markers. In addition, we determined if any association exists between polymorphisms in the TGF-beta 1 gene and atherosclerosis in South African CKD patients. Methods. We studied 120 CKD patients and 40 healthy controls. Serum TGF-beta 1, TGF-beta 2, TGF-beta 3, endotoxin, and inflammatory markers were measured. Functional polymorphisms in the TGF-beta 1 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-beta isoforms levels were significantly lower in the patients with atherosclerosis compared to patients without atherosclerosis (p<0.001). Overall, TGF-beta isoforms had inverse relationships with CIMT. TGF-beta 1 and TGF-beta 2 levels were significantly lower in patients with carotid plaque compared to those without carotid plaque [TGF-beta 1: 31.9 (17.2-42.2) versus 45.9 (35.4-58.1) ng/ml, p=0.016; and TGF-beta 2: 1.46 (1.30-1.57) versus 1.70 (1.50-1.87) ng/ml, p=0.013]. In multiple logistic regression, age, TGF-beta 2, and TGF-beta 3 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-beta 2: OR, 0.996; 95% CI: 0.994-0.999, p=0.018; TGF-beta 3: OR, 0.992; 95% CI: 0.985-0.999, p=0.029). TGF-beta 1 genotypes did not influence serum levels of TGF-beta 1 and no association was found between the TGF-beta 1 gene polymorphisms and atherosclerosis risk. Conclusion. TGF-beta isoforms seem to offer protection against the development of atherosclerosis among South African CKD patients.