Vitamin D metabolism in peripheral blood mononuclear cells is influenced by chewing Betel nut (Areca catechu) and vitamin D status

Context: Vitamin D deficiency, common in South Asians, is a risk factor for metabolic syndrome, type 2 diabetes, and ischemic heart disease. Vitamin D receptor (VDR) activation depends on activated vitamin D [1,25-dihydroxyvitamin D (1,25(OH)(2)D)] concentration, reflecting opposing actions of 25-hydroxyvitamin D-1 alpha-hydroxylase [1-alpha(OH)ase] for formation and 25(OH)D-24-hydroxylase [24( OH) ase] for catabolism. We previously reported that circulating 1,25(OH) 2D contributed to determination of VDR-protein levels and VDR genotype was a determinant of both VDR mRNA and VDR-protein in South Asians. Objective: We hypothesized that chewing betel nut, an addictive habit common throughout South Asian communities, contributes to hypovitaminosis-D by modulating the enzymes regulating circulating 1,25(OH) 2D concentration. Design: Peripheral blood mononuclear cell (PBMC) 1-alpha(OH) ase and 24(OH) ase mRNA concentrations were measured and examined in relation to cross-sectional data on the vitamin-D axis, diet, smoking, and betel usage, including PBMC VDR-RNA and VDR-protein content in a pilot study of 33 healthy British Bangladeshis. Results: PBMC 24( OH) ase mRNA correlated positively and serum 1,25(OH) 2D negatively with betel quids per day (r = 0.49, P = 0.006 and r = - 0.486, P = 0.006, respectively). Independent determinants for 24(OH) ase included betel quids per day (P < 0.0001) and serum 25-OHD (P = 0.024). Independent determinants for serum 1,25(OH) 2D were gender, smoking, and betel quids per day. PBMC 1-alpha(OH) ase mRNA correlated inversely with VDR mRNA (r = - 0.44; P = 0.013); its independent determinants were serum 1,25(OH) 2D and VDR TaqI and BsmI polymorphisms (P = 0.03-0.0001). Conclusions: Betel chewing is a more powerful independent determinant of increased 24(OH) ase expression and of decreased serum calcitriol than serum 25-OHD, supporting the hypothesis that this habit could aggravate the effects of vitamin-D deficiency.