Transforming Growth Factor- Protects against Inflammation-Related Atherosclerosis in South African CKD Patients.

BACKGROUND

Transforming growth factor- (TGF-) may inhibit the development of atherosclerosis. We evaluated serum levels of TGF- isoforms concurrently with serum levels of endotoxin and various inflammatory markers. In addition, we determined if any association exists between polymorphisms in the gene and atherosclerosis in South African CKD patients.

METHODS

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

CONCLUSION

TGF- isoforms seem to offer protection against the development of atherosclerosis among South African CKD patients.