Investigation of the association of BMP gene variants with nephropathy in Type 1 diabetes mellitus

A. J. McKnight, K. A. Pettigrew, C. C. Patterson, J. Kilner, D. M. Sadlier, A. P. Maxwell, Warren 3 UK GoKinD Study Grp

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Aims Diabetic nephropathy is a leading cause of end-stage renal disease. The transforming growth factor beta-bone morphogenic protein (BMP) pathway is implicated in the pathogenesis of diabetic nephropathy. The BMP2, BMP4 and BMP7 genes are located near linkage peaks for renal dysfunction, and we hypothesize that genetic polymorphisms in these biological and positional candidate genes may be risk factors for diabetic kidney disease.

Methods The BMP7 gene was screened, variants identified and allele frequencies determined by bidirectionally sequencing 46 individuals to facilitate selection of tag SNPs (n = 4). For BMP2 and BMP4 genes, data were downloaded for 19 single nucleotide polymorphisms (SNPs) from the International HapMap project and six tag SNPs selected.

Results The BMP7 gene was screened for novel genetic polymorphisms, haplotypes were identified, an appropriate subset of variants selected for the investigation of common genetic risk factors, and BMP2, BMP4 and BMP7 genes assessed for association with diabetic nephropathy in 1808 individuals. Thirty-two SNPs were identified, of which 11 were novel, including an amino-acid changing SNP ((+)63639C>T). No significant differences (P > 0.2) were observed when comparing genotype or allele or haplotype frequencies between 864 individuals with Type 1 diabetes and nephropathy compared with 944 individuals with Type 1 diabetes without nephropathy, stratified by recruitment centre.

Conclusions Common polymorphisms in these BMP genes do not strongly influence genetic susceptibility to diabetic nephropathy in White individuals with Type 1 diabetes mellitus.

Original languageEnglish
Pages (from-to)624-630
Number of pages7
JournalDiabetic Medicine
Volume27
Issue number6
DOIs
Publication statusPublished - Jun 2010

Keywords

  • association
  • bone morphogenic protein
  • genetic predisposition
  • kidney
  • single nucleotide polymorphism
  • BONE MORPHOGENETIC PROTEIN-7
  • DNA POLYMORPHISMS
  • MESANGIAL CELLS
  • HIGH GLUCOSE
  • PREDISPOSITION
  • PODOCYTES
  • DISEASE
  • MAPS

Fingerprint

Dive into the research topics of 'Investigation of the association of BMP gene variants with nephropathy in Type 1 diabetes mellitus'. Together they form a unique fingerprint.

Cite this