Vitamin D Receptor (VDR) mRNA and VDR Protein Levels in Relation to Vitamin D Status, Insulin Secretory Capacity, and VDR Genotype in Bangladeshi Asians
Author:
Ogunkolade Babatunji-William1, Boucher Barbara J.1, Prahl Jean M.2, Bustin Stephen A.3, Burrin Jacky M.4, Noonan Kate5, North Bernard V.6, Mannan Nassima1, McDermott Michael F.1, DeLuca Hector F.2, Hitman Graham A.1
Affiliation:
1. Department of Diabetes and Metabolic Medicine, Barts and the London Queen Mary’s School of Medicine and Dentistry, University of London, London 2. Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 3. Department of Surgery, Barts and the London Queen Mary’s School of Medicine and Dentistry, University of London, London 4. Department of Endocrinology, Barts and the London Queen Mary’s School of Medicine and Dentistry, University of London, London 5. Department of Clinical Biochemistry, Barts and the London Queen Mary’s School of Medicine and Dentistry, University of London, London 6. Department of Psychiatry, Barts and the London Queen Mary’s School of Medicine and Dentistry, University of London, London, U.K.
Abstract
Associations have been reported between vitamin D receptor (VDR) gene polymorphisms, type 1 diabetes, insulin secretion, and the insulin resistance syndrome. As VDR polymorphisms have no known functional significance, these findings may implicate a variant of the VDR gene or a locus in linkage disequilibrium with the VDR. We have examined VDR mRNA and VDR protein levels in relation to VDR polymorphisms (41 Bangladeshi subjects) and analyzed insulin secretory capacity (143 Bangladeshi subjects), allowing for other known determinants. Peripheral blood mononuclear cells (PBMCs) from subjects who had been genotyped for BsmI, ApaI, TaqI, and FokI VDR restriction fragment length polymorphisms were used for both total VDR mRNA quantitation (using TaqMan) and measurement of VDR protein levels (using a specific micro-immunoassay). Stepwise multiple regression analyses were used (to P < 0.05) to analyze the data. For the insulin secretion index, the best-fit model (n = 143, P < 0.0001) gave age (P = 0.002), TaqI (P < 0.0001), and BMI (P = 0.001) as independent determinants; with the inclusion of VDR mRNA and VDR protein levels, VDR mRNA was the sole independent determinant (n = 41, P = 0.024). However, the best-fit model for VDR mRNA (P = 0.004) gave FokI (P = 0.044) and TaqI (P = 0.04) genotypes and insulin secretory capacity (P = 0.042) as independent determinants. For VDR protein levels, the best-fit model (P = 0.006) gave TaqI genotype (P = 0.005) and circulating 1,25-dihydroxyvitamin-D levels (P = 0.03) as independent determinants. In conclusion, these studies confirm an association between VDR polymorphisms and insulin secretory capacity and demonstrate the VDR genotype to be a significant determinant of VDR mRNA and VDR protein levels in PBMCs, providing functional support to previously described genetic associations with the VDR gene. Furthermore, VDR expression has been shown to be a determinant of insulin secretory capacity.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Reference58 articles.
1. DeLuca HF: The metabolism, physiology and function of vitamin D. In Vitamin D, Basic and Clinical Aspects. Kumar R, Ed. Boston, MA, Nijhoff Publishing, 1984, p.259–302 2. Holick MF: Noncalcemic actions of 1,25-dihydroxyvitamin D3 and clinical applications. Bone 17:107S–111S, 1995 3. MacDonald PN: Molecular biology of the vitamin D receptor. In Vitamin D. Physiology, Molecular Biology, and Clinical Applications. Holick MF, Ed. Boston, MA, Humana Press, 1999, p.109–128 4. Pike JW: The vitamin D receptor and its gene. In Vitamin D. Feldman D, Glorieux FH, Pike JW, Eds. San Diego, CA, Academic Press, 1997, p.105–125 5. Zmuda JM, Cauley JA, PH, Ferrell RE: Molecular epidemiology of vitamin D receptor gene variants. Epidemiol Rev 22:203–217, 2000
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