Transforming Growth Factor-<i>β</i> Protects against Inflammation-Related Atherosclerosis in South African CKD Patients

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- β 1 gene and atherosclerosis in South African CKD patients. Methods . We studied 120 CKD patients and 40 healthy controls. Serum TGF- β 1, TGF- β 2, TGF- β 3, endotoxin, and inflammatory markers were measured. Functional polymorphisms in the TGF- β 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- β isoforms levels were significantly lower in the patients with atherosclerosis compared to patients without atherosclerosis (p&lt;0.001). Overall, TGF- β isoforms had inverse relationships with CIMT. TGF- β 1 and TGF- β 2 levels were significantly lower in patients with carotid plaque compared to those without carotid plaque [TGF- β 1: 31.9 (17.2 – 42.2) versus 45.9 (35.4 – 58.1) ng/ml, p=0.016; and TGF- β 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- β 2, and TGF- β 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- β 2: OR, 0.996; 95% CI: 0.994–0.999, p=0.018; TGF- β 3: OR, 0.992; 95% CI: 0.985–0.999, p=0.029). TGF- β 1 genotypes did not influence serum levels of TGF- β 1 and no association was found between the TGF- β 1 gene polymorphisms and atherosclerosis risk. Conclusion. TGF- β isoforms seem to offer protection against the development of atherosclerosis among South African CKD patients.