Osteoarthritis Research Today is a free monthly online journal that collates and summarizes the latest research about Osteoarthritis, including details on treatment, symptoms, causes, medication.

Strong linkage on 2q33.3 to familial early-onset generalized osteoarthritis and a consideration of two positional candidate genes.

Meulenbelt I, Min JL, van Duijn CM, Kloppenburg M, Breedveld FC, Slagboom PE

Molecular Epidemiology, Leiden University Medical Center, Einthovenweg 20, 2300 RC Leiden, The Netherlands. i.meulenbelt@lumc.nl

A genomewide screen was performed in four extended families with early-onset generalized osteoarthritis (FOA) without dysplasia. The FOA phenotype within these families shows a dominant Mendelian inheritance pattern and may represent common osteoarthritis (OA) at later ages. An initial locus was confirmed by three additional families and refined by 14 markers to a two-point logarithm of odds score of 6.05 (theta=0.00) for marker D2S155 at chromosome 2q33.3. This locus coincided with the highest multipoint nonparametric linkage score of 4.70 (P-value=0.0013) at marker D2S2358. Haplotype analysis of family members delineated a narrow region with a number of possible positional candidates, of which we investigate here the two most likely ones: PTHR2, encoding parathyroid hormone receptor 2, and FZD5, encoding frizzled receptor 5. For FZD5, we did not observe a segregating variant, however, for PTHR2, a missense variant (A225S) cosegregated with FOA in one family. The frequency of the PTHR2 variant was rare in a population-based sample, aged 55-70 years (N=1228, 0.4%). Of the 11 carriers, 36% showed generalized radiographic OA as compared to 23% in the remaining population. None of the other families that contributed to the linkage revealed a segregating variant. Together, we have identified a locus on chromosome 2q33.3 for FOA. Candidate gene analysis suggested a possible association of a PTHR2 variant with generalized radiographic OA; it is, however, unlikely the major disease gene for the observed linkage to the FOA phenotype.

Published 23 November 2006 in Eur J Hum Genet, 14(12): 1280-7.
Full-text of this article is available online (may require subscription).

© 2004-2008 Osteoarthritis Research Today. All Rights Reserved.