Haplotypes of the low-density lipoprotein receptor-related protein 5 (LRP5) gene: are they a risk factor in osteoarthritis?
OBJECTIVE
Several genome-wide scans have revealed an osteoarthritis (OA)-susceptibility locus on chromosome 11q in close proximity to the low-density lipoprotein receptor-related protein 5 (LRP5) gene. The regulation of bone mass is under the control of LRP5 and since increased bone mass is thought to play a role in the pathology of OA we examined LRP5 polymorphisms and haplotypes to determine if variants of this locus may predispose to OA.


METHODS
A UK control population of 187 individuals was examined for five commonly occurring polymorphisms against a cohort of 158 DNAs from patients with knee OA. An additional UK cohort was also examined to confirm the findings of the first study; this second group consisted of 110 knee OA patients. Haplotype analysis was also performed on patient and control DNAs.


RESULTS
A study of individual polymorphisms revealed no association with disease. However, haplotype analysis of the initial two populations revealed a common haplotype (C-G-C-C-A) that provided a 1.6-fold increased risk of OA (P(c)=0.021). The data obtained from the second cohort confirmed the initial findings, with a 1.6-fold increased risk observed within this cohort for the risk haplotype (P=0.012).


CONCLUSIONS
A closer investigation of LRP5 and associated Wnt signalling molecules in OA will help determine disease aetiology and the development of novel treatment strategies that specifically target the bone compartment.
Smith
A J P
AJ
University of Bristol Department of Pathology and Microbiology, Homoeopathic Hospital Site, Cotham, Bristol BS6 6JU, UK.
Gidley
J
J
Sandy
J R
JR
Perry
M J
MJ
Elson
C J
CJ
Kirwan
J R
JR
Spector
T D
TD
Doherty
M
M
Bidwell
J L
JL
Mansell
J P
JP
D000368:Aged; D015519:Bone Density / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D026502:LDL-Receptor Related Proteins; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011973:Receptors, LDL / Q000235:genetics*; D006113:United Kingdom
D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D011973:Receptors, LDL