HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ogunkolade, B.-W. Articles by Hitman, G. A. Search for Related Content PubMed PubMed Citation Articles by Ogunkolade, B.-W. Articles by Hitman, G. A. Social Bookmarking                What's this?

Vitamin D Receptor (VDR) mRNA and VDR Protein Levels in Relation to Vitamin D Status, Insulin Secretory Capacity, and VDR Genotype in Bangladeshi Asians

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 Surgery, Barts and the London Queen Mary’s School of Medicine and Dentistry, University of London, London
³ Department of Endocrinology, Barts and the London Queen Mary’s School of Medicine and Dentistry, University of London, London
⁴ Department of Clinical Biochemistry, Barts and the London Queen Mary’s School of Medicine and Dentistry, University of London, London
⁵ Department of Psychiatry, Barts and the London Queen Mary’s School of Medicine and Dentistry, University of London, London, U.K.
⁶ Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin

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.

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				E. S. Kang, M. S. Kim, Y. S. Kim, C. H. Kim, S. J. Han, S. W. Chun, K. Y. Hur, C. M. Nam, C. W. Ahn, B. S. Cha, et al. A Polymorphism in the Zinc Transporter Gene SLC30A8 Confers Resistance Against Posttransplantation Diabetes Mellitus in Renal Allograft Recipients Diabetes, April 1, 2008; 57(4): 1043 - 1047. [Abstract] [Full Text] [PDF]

				S.-W. Guo, V. L. Magnuson, J. J. Schiller, X. Wang, Y. Wu, and S. Ghosh Meta-Analysis of Vitamin D Receptor Polymorphisms and Type 1 Diabetes: A HuGE Review of Genetic Association Studies Am. J. Epidemiol., October 15, 2006; 164(8): 711 - 724. [Abstract] [Full Text] [PDF]

				E. RAMOS-LOPEZ, T. JANSEN, V. IVASKEVICIUS, H. KAHLES, C. KLEPZIG, J. OLDENBURG, and K. BADENHOOP Protection From Type 1 Diabetes by Vitamin D Receptor Haplotypes Ann. N.Y. Acad. Sci., October 1, 2006; 1079(1): 327 - 334. [Abstract] [Full Text] [PDF]

				W. B. Ogunkolade, B. J. Boucher, S. A. Bustin, J. M. Burrin, K. Noonan, N. Mannan, and G. A. Hitman Vitamin D Metabolism in Peripheral Blood Mononuclear Cells Is Influenced by Chewing "Betel Nut" (Areca catechu) and Vitamin D Status J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2612 - 2617. [Abstract] [Full Text] [PDF]

				W G. John, K. Noonan, N. Mannan, and B. J Boucher Hypovitaminosis D is associated with reductions in serum apolipoprotein A-I but not with fasting lipids in British Bangladeshis Am. J. Clinical Nutrition, September 1, 2005; 82(3): 517 - 522. [Abstract] [Full Text] [PDF]

				M. J. Taverna, J.-L. Selam, and G. Slama Association between a Protein Polymorphism in the Start Codon of the Vitamin D Receptor Gene and Severe Diabetic Retinopathy in C-Peptide-Negative Type 1 Diabetes J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4803 - 4808. [Abstract] [Full Text] [PDF]

				R. Scragg, M. Sowers, and C. Bell Serum 25-Hydroxyvitamin D, Diabetes, and Ethnicity in the Third National Health and Nutrition Examination Survey Diabetes Care, December 1, 2004; 27(12): 2813 - 2818. [Abstract] [Full Text] [PDF]

				G. D. Smith and S. Ebrahim Mendelian randomization: prospects, potentials, and limitations Int. J. Epidemiol., February 1, 2004; 33(1): 30 - 42. [Full Text] [PDF]

				P.M. Timms, N. Mannan, G.A. Hitman, K. Noonan, P.G. Mills, D. Syndercombe-court, E. Aganna, C.P. Price, and B.J. Boucher Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? QJM, December 1, 2002; 95(12): 787 - 796. [Abstract] [Full Text] [PDF]