Single Nucleotide Polymorphisms in Promoter Region of Tgf-β1 Gene Distinguish African Americans from Caucasians: A Possible Genetic Basis for Racial Differences in Epidemiology of Hypertension and End Stage Renal Disease.
Transforming growth factor-beta 1 (TGF-β1) excess is a candidate risk factor for hypertension and hypertensive complications including LVH, vascular remodeling and end stage renal disease (ESRD). We reported that hyperexpression of TGF-β1 protein is more prevalent in African Americans (AA) compared with Caucasians (C), particularly AA with hypertension and/or ESRD. Single nucleotide polymorphisms (SNPs) have been reported in the TGF-β1 gene, and there is evidence for heritable control of TGF-β1 protein levels. In this study we tested the hypothesis that TGF-β1 SNPs distinguish AA from C. We determined the frequencies of all 6 known biallelic TGF-β1 DNA polymorphisms in 793 subjects (AA=342 [normal: 77, hypertension: 66, ESRD: 199], C=451 [normal: 142, hypertension: 81, ESRD: 228]). SNPs as well as cis/trans combination of alleles (haplotypes) were identified by designing and using allele specific primers in an amplification refractory mutation system PCR . Our data demonstrate that SNPs at -800bp and -509bp and the haplotype frequencies (GC, GT, AC, AT) are significantly different between AA and C (Table). In conclusion, genetically determined differences in TGF-β1 production may explain TGF-β1 excess in AA as well as provide a molecular basis for the excess burden of hypertension and hypertensive complications in AA.