Microsatellite association mapping of a primary osteoarthritis susceptibility locus on chromosome 6p12.3-q13.
OBJECTIVE
To test a high density of microsatellite markers from within a primary osteoarthritis (OA) locus on chromosome 6 for association with OA as a means of narrowing and focusing our search for the susceptibility gene.


METHODS
One hundred forty-six families, each with 2 or more women concordant for primary OA (ascertained by total hip replacement), were genotyped for 36 microsatellite markers from within a narrow interval at 6p12.3-q13 which we had previously shown to be linked to OA. Each marker was tested for linkage and for association, the latter by means of the transmission disequilibrium test and by a case-control analysis.


RESULTS
The highest 2-point logarithm of odds (LOD) score was 4.8, with 11 markers having LOD scores > or =2.0. Several markers demonstrated evidence of association, in particular, a cluster of markers positioned within or near the functional candidate gene BMP5.


CONCLUSIONS
Our linkage data reinforce the evidence of a major susceptibility locus on chromosome 6. We had previously failed to detect an association with BMP5 using gene-based single-nucleotide polymorphisms. The association data reported here prompt us to speculate that the chromosome 6 susceptibility may be coded for by cis-acting polymorphism in the regulatory elements of this gene, rather than by variation in its protein coding sequence.
Southam
Lorraine
L
University of Oxford, Oxford, UK.
Dowling
Barbara
B
Ferreira
Athena
A
Marcelline
Lucy
L
Mustafa
Zehra
Z
Chapman
Kay
K
Bentham
Graham
G
Carr
Andrew
A
Loughlin
John
J
D019644:Arthroplasty, Replacement, Hip; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats; D015207:Osteoarthritis, Hip / Q000235:genetics* / Q000601:surgery; D016133:Polymerase Chain Reaction