Skip Navigation



NDT Advance Access published online on September 27, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp515
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Martin, R. J. L.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Martin, R. J. L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press [on behalf of ERA-EDTA]. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


A rare haplotype of the vitamin D receptor gene is protective against diabetic nephropathy

Rosalind J. L. Martin1, Amy J. McKnight1, Christopher C. Patterson2, Denise M. Sadlier3, Alexander P. Maxwell1 The Warren 3/UK GoKinD Study Group

1 Nephrology Research Group 2 Epidemiology Research Group, Queen's University of Belfast, Northern Ireland 3 Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Republic of Ireland

Correspondence and offprint requests to: Rosalind J. L. Martin; E-mail: nephres{at}qub.ac.uk



  Abstract

Background. Vitamin D and its analogues are reported to have renoprotective effects in chronic kidney disease including diabetic nephropathy (DN). Vitamin D3 is converted to 1,25(OH)D3 by CYP2R1 and CYP27B1. The biological action of 1,25(OH)D3 is mediated via its receptor. VDR, CYP27B1 or CYP2R1 gene variants could modify the biological activity of vitamin D3. We have conducted the first case-control association study to determine the relationship between polymorphisms in VDR, CYP27B1 and CYP2R1 genes, and the risk of DN in individuals with type 1 diabetes.

Methods. Eight VDR single-nucleotide polymorphisms (SNPs) rs10735810 FokI C>T, rs1544410 BsmI G>A, rs7975232 ApaI G>T, rs731236 TaqI T>C, rs4303288 G>T, rs11168275 C>T, rs12721366 G>A and rs2544043 G>C were investigated with CYP27B1 rs4646536 T>C and CYP2R1 rs10741657 G>A. Genotyping was performed using pyrosequencing, Taqman, Sequenom or direct sequencing technologies in 1329 type 1 diabetics (655 nephropaths, 674 non-nephropaths).

Results. No significant differences were observed in genotype or allele frequencies between case and control groups for VDR, CYP27B1 or CYP2R1 SNPs, either before or after stratification by recruitment centre or when restricted to patients with end-stage renal disease. A previously identified haplotype block from rs1544410 to rs731236 was confirmed at the 3'-end of VDR. Comparison of haplotype frequencies identified the rare AGT haplotype as significantly protective against DN, 3.1% cases versus 5.8% controls; {chi}2 = 11.05, Pc = 0.009 by the permutation test.

Conclusions. Our study has identified a rare VDR haplotype that is protective against DN in patients with type 1 diabetes. Replication in a large, independent cohort is required to confirm this finding.

Keywords: diabetic nephropathy; haplotype; SNP; VDR

Received for publication: 16. 6.09
Accepted in revised form: 2. 9.09


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.