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.
University of Bristol Department of Pathology and Microbiology, Homoeopathic Hospital Site, Cotham, Bristol BS6 6JU, UK.
A J P
AJ
Smith
J
J
Gidley
J R
JR
Sandy
M J
MJ
Perry
C J
CJ
Elson
J R
JR
Kirwan
T D
TD
Spector
M
M
Doherty
J L
JL
Bidwell
J P
JP
Mansell
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