Association study of candidate genes for the progression of hand osteoarthritis.
OBJECTIVE
Although a few consistent osteoarthritis (OA) susceptibility genes have been identified, little is known on OA progression. Since OA progression is clinically the most relevant phenotype, we investigate the association between asporin (ASPN), bone morphogenetic protein 5 (BMP5) and growth differentiation factor 5 (GDF5) polymorphisms and progression of hand OA.


METHODS
Single-nucleotide polymorphisms (SNPs) ASPN rs13301537, BMP5 rs373444 and GDF5 rs143383 were genotyped in 251 hand OA patients from the Genetics osteoARthritis and Progression (GARP) study and 725 controls. In a case-control comparison we assessed the association between these SNPs and radiographic progression of hand OA over 6 years, which was based on change in osteophytes or joint space narrowing (JSN), above the smallest detectable change. SNPs with suggestive evidence for association were further analysed for their effect on progression over 2 years, and for the mean change in osteophytes and JSN.


RESULTS
The minor allele of ASPN SNP rs13301537 was associated with hand OA progression over 6 years (odds ratio (OR) (95% CI) 1.49 (1.06-2.07); P = 0.020). The mean change in osteophytes and JSN was higher in carriers of the minor allele compared to homozygous carriers of the common allele with mean difference of 0.73 (95% CI - 0.07-1.56; P = 0.073) and 0.82 (95% CI 0.12-1.52; P = 0.022), respectively. An association with similar effect size was found between ASPN SNP rs13301537 and 2-year progression, and the mean change in osteophytes and JSN was significantly higher in homozygotes.


CONCLUSIONS
ASPN is associated with hand OA progression. This gives insight in the pathogenesis of hand OA progression and identified a potential target for therapeutic approaches.
Department of Rheumatology, Leiden University Medical Center, The Netherlands. J.Bijsterbosch@lumc.nl
J
J
Bijsterbosch
M
M
Kloppenburg
M
M
Reijnierse
F R
FR
Rosendaal
T W J
TW
Huizinga
P E
PE
Slagboom
I
I
Meulenbelt
D000368:Aged; D055417:Bone Morphogenetic Protein 5 / Q000235:genetics; D016022:Case-Control Studies; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055428:Growth Differentiation Factor 5 / Q000235:genetics; D050823:Hand Joints / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D054850:Osteophyte / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011859:Radiography
C439889:ASPN protein, human; C525814:BMP5 protein, human; D055417:Bone Morphogenetic Protein 5; D016326:Extracellular Matrix Proteins; C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5