Epigenetic regulation of vitamin D converting enzymes.

ABSTRACT

While 25-OH-D3 serum levels in humans undergo a large seasonal variation, 1,25-(OH)2-D3 is regulated within a narrow range. We speculate that in addition to the known genomic and nongenomic regulation there could be further epigenetic mechanisms involved. We annotated the human CYP27B1 (alpha-1-hydroxylase) and CYP24A1 (24-hydroxylase) genes for CpG islands and sequenced these in bisulfite treated DNA extracted of peripheral blood lymphocytes from 384 individuals. 40 CpG sites could be analyzed, of these 15 in CYP27B1 and 25 in CYP24A1. The average methylation ratio (MR) in CYP27B1 was 11% (s.d. 5%) with the highest ratio observed in exon 1 (38%). CYP24A1 showed only a 6.5% MR (s.d. 5%). Neither CYP24A1 nor CYP27B1 MR correlated with season of examination date nor with current 25-OH-D3 and 1,25-(OH)2-D3 serum levels except of a weak association of three consecutive CYP27B1 CpG sites and 25-OH-D3 levels. In summary, human PBLs showed only weak methylation in the upstream region of CYP27B1 and none in CYP24A1. As PBLs represent an heterogeneous pool of cells, a further analysis of the seasonal methylation pattern in B or T cell subsets (or other tissues like liver or kidney) is warranted including an extended coverage of the CYP27B1 promotor.