A common functional C-T substitution polymorphism in the promoter region of the human catalase gene influences transcription factor binding, reportergene transcription and is correlated to blood catalase levels

Oxidative stress is implicated in disease and aging. In order to obtain mol ecular genetic tools that can be used to determine the potential impact of oxidative stress we examined the human catalase gene promoter for possible variation. Genomic DNA isolated from 10 individuals was screened for polymo rphisms in the 5'-flanking region by direct sequence analysis of PCR produc ts (nt -307 to -46 from the transcription start site). A common C/T polymor phism -262 base pairs from the transcription start site was detected. Compu ter analysis indicated that the two variants bound different transcription factors. Indeed, gel retardation analysis revealed different protein bindin g patterns to the two variants. Expression studies with reporter constructs showed significantly higher transcriptional activity of the T variant in H epG2 and K562 cells (1.5-fold, p < .05 Wilcoxon test), Thus a higher expres sion in human liver and blood cells is possible. In order to test this hypo thesis, catalase levels in red blood cells were determined in 29 donors. Th e corresponding genotype was determined with a restriction enzyme-based ass ay. It was found that catalase levels were significantly higher in donors c arrying the T allele in comparison to donors homozygous for the C allele (p < .03). In conclusion, we report here the first common (allele frequency i n a Swedish population, 28%) genetic variant in a fundamental oxidative str ess protection gene with a defined phenotype. (C) 2001 Elsevier Science Inc .