Protective effect of high levels of TGF-β1 cytokine and its corresponding allele at C-509T locus in Punjabi ESRD population

Abstract

End Stage Renal Disease (ESRD) is a chronic inflammatory condition when the kidney function has diminished to <10% of its normal capacity. In contrast to most of the reports from the west, our earlier study on Punjabi population documented lower circulating levels of transforming growth factor-β1 (TGF-β1) in ESRD patients as compared to their age and sex matched healthy controls. This prompted us to investigate the correlation between circulating TGF-β1 protein levels and C-509 T promoter polymorphism (rs1800469) in Punjabi ESRD population. A total of 192 ESRD (77 diabetic ESRD and 115 hypertensive ESRD) and 130 normal healthy controls, participated in this study. Genotyping of C-509 T polymorphism was done with Amplification Refractory Mutation System Analysis (ARMS–PCR) and circulating TGF-β1 levels were measured with ELISA. Diabetic ESRD group revealed significantly different allele frequencies from normal population (χ2 = 4.615; p = .032). Also, levels of TGF-β1 cytokine were significantly depleted between diabetic (11.44 ± 7.79 ng/ml) as well as hypertensive (8.68 ± 6.54 ng/ml) ESRD patients as compared to their normal counterparts (26.09 ± 10.73 ng/ml). A comparison of mean TGF-β1 protein levels among individuals carrying CC, CT and TT genotypes within diabetic ESRD (p = .561) and hypertensive ESRD population (p = .221) did not present any association. We submit the first report on the correlation between TGF-β1 C-509 T polymorphism with its corresponding circulating levels in north India Punjabi population. Our results suggest a protective effect of T allele against developing ESRD within Punjabi diabetic population [odds ratio = 0.63 (CI = 0.41–0.96)]. It also suggests that TGF-β1 does not play its anticipated pro-fibrotic role but perhaps mediates an equally important anti-inflammatory function.