Absence of linkage or association for osteoarthritis with the vitamin D receptor/type II collagen locus: the Framingham Osteoarthritis Study.
OBJECTIVE
Studies have suggested that polymorphisms or mutations either in the COL2A1 or VDR gene. both on chromosome 12q, are associated with the occurrence of osteoarthritis (OA). We examined linkage and association between the VDR/COL2A1 locus and hand/knee OA in the Framingham Osteoarthritis Study (FOS).


METHODS
Hand and knee joints were characterized radiographically in the FOS. An overall score for OA using the standard Kellgren and Lawrence grading scheme was determined, as well as scores for individual features of OA including osteophytes and joint space narrowing. For linkage studies, polymorphic microsatellite markers near the VDR-COL2AI genes on chromosome 12 were tested in a collection of 296 of the largest Framingham Heart Study families and the results analyzed using variance component linkage (SOLAR). For association studies, we characterized the allele status of a subset of subjects at the BsmI site of the VDR gene.


RESULTS
Overall, we found no linkage or association between OA and the COL2A1/VDR locus for either knee or hand OA, nor did we find an association or linkage between COL2AI or VDR with any individual radiographic features of OA.


CONCLUSIONS
Despite studies suggesting associations of OA with both COL2A1 and VDR loci, our results suggest that mutations at the COL2A1/VDR locus do not play an important role as a cause of common OA in the population at large.
Baldwin
Clinton T
CT
Boston University Arthritis Center, Department of Medicine and Neurology, Boston University School of Medicine, MA 02118, USA.
Cupples
L Adrienne
LA
Joost
Oscar
O
Demissie
Serkalem
S
Chaisson
Christine
C
Mcalindon
Timothy
T
Myers
Richard H
RH
Felson
David
D
D000368:Aged; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D015331:Cohort Studies; D024043:Collagen Type II / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005384:Finger Joint / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005787:Gene Frequency / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011110:Polymorphism, Genetic / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012737:Sex Factors
D024043:Collagen Type II; D018167:Receptors, Calcitriol