Aggrecan core protein of a certain length is protective against hand osteoarthritis.
OBJECTIVE
To study the contribution of aggrecan VNTR (variable number of tandem repeats) polymorphism to clinically differing manifestations of hand osteoarthritis (OA).


METHODS
Five hundred thirty Finnish females representing two academically similar occupations with completely diverse exposure to hand load were included. Radiographs of hands were analysed, the OA findings were graded and the subjects were divided into categories. Aggrecan VNTR alleles were identified by Southern hybridization. Statistical analyses were used to compare joint involvement and pathological findings with the prevalences of the alleles and genotypes.


RESULTS
Subjects homozygous for the most common aggrecan VNTR allele, A27 with 27 repeats, had a significantly lower risk of hand OA, with OR 0.46 (95% CI 0.27-0.78) for OA of grade 2 or more. Our results suggest that carrying two copies of the alleles with less than 27 repeats could predispose a subject to a severe hand OA (OR 2.45, 95% CI 1.17-5.12) and carrying two copies of the alleles with more than 27 repeats also increases the risk of the disease (OR 1.73, 95% CI 1.03-2.89).


CONCLUSIONS
These findings indicate that allele A27 provides protection from hand OA and that alleles shorter or longer than this may predispose subjects to the disease. Furthermore, they suggest that a certain number of tandem repeats provide for optimal functioning of the aggrecan molecule and that the contribution of genetic factors to the development of hand OA may be even more important than that of environmental factors.
Kämäräinen
O-P
OP
Collagen Research Unit, Biocenter and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland.
Solovieva
S
S
Vehmas
T
T
Luoma
K
K
Leino-Arjas
P
P
Riihimäki
H
H
Ala-Kokko
L
L
Männikkö
M
M
D053674:Aggrecans / Q000235:genetics*; D005260:Female; D005387:Finland; D006225:Hand / Q000000981:diagnostic imaging; D006801:Humans; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011859:Radiography
D053674:Aggrecans