Vitamin D Metabolism in Peripheral Blood Mononuclear Cells Is Influenced by Chewing “Betel Nut” (Areca catechu) and Vitamin D Status

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Abstract
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)2D)] concentration, reflecting opposing actions of 25-hydroxyvitamin D-1α-hydroxylase [1-α(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-α(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-α(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.

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