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

Centers for Diabetes and Metabolic Medicine and Academic Surgery, Institute of Cell and Molecular Science (W.B.O., B.J.B., S.A.B., N.M., G.A.H.), and Clinical and Molecular Endocrinology, William Harvey Institute (J.M.B.), Queen Mary’s School of Medicine and Dentistry, University of London and Department of Clinical Chemistry (K.N.), Barts and The London National Health Service Trust, Royal London Hospital, London E1 1BB, United Kingdom

Address all correspondence and requests for reprints to: Graham A. Hitman, M.D., Center for Diabetes and Metabolic Medicine, Royal London Hospital, London E1 1BB, United Kingdom. E-mail: g.a.hitman{at}qmul.ac.uk.

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-1-hydroxylase [1-(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-(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-(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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