Investigation of the association of BMP gene variants with nephropathy in Type 1 diabetes mellitus.
OBJECTIVE
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.
McKnight
A J
AJ
Nephrology Research Group, Queen's University of Belfast, Belfast, UK. a.j.mcknight@qub.ac.uk
Pettigrew
K A
KA
Patterson
C C
CC
Kilner
J
J
Sadlier
D M
DM
Maxwell
A P
AP
D000328:Adult; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins