Investigating the aspartic acid (D) repeat of asporin as a risk factor for osteoarthritis in a UK Caucasian population.
OBJECTIVE
A compelling genetic association with osteoarthritis (OA) of 2 functional alleles in the aspartic acid (D) repeat of the asporin gene was recently reported in a Japanese population. Allele D13 of the repeat encoded OA protection, whereas allele D14 encoded OA susceptibility. The 2 alleles mediate differences in the capacity of asporin to inhibit the cartilage growth factor transforming growth factor beta, with the D14 allele being a particularly potent inhibitor. Our objective was to assess whether the D repeat is associated with OA in UK Caucasians.


METHODS
The repeat was genotyped in 1,247 patients who had undergone elective joint replacement of the hip or the knee due to end-stage primary OA and in 748 age-matched controls.


RESULTS
The D13 allele was more common in controls, and the D14 allele was more common in patients. However, this trend was significant only for men who had undergone hip replacement (P = 0.016, odds ratio 1.48, 95% confidence interval 1.09-2.01).


CONCLUSIONS
Our data suggest that the asporin polymorphism is not a major influence on OA etiology in Caucasians. The results of our study do not question the veracity of the Japanese report. Instead, our study highlights the complex, heterogeneous nature of OA genetic susceptibility.
Mustafa
Zehra
Z
Botnar Research Centre, Institute of Musculoskeletal Sciences, Nuffield Orthopaedic Centre, University of Oxford, Oxford OX3 7LD, UK.
Dowling
Barbara
B
Chapman
Kay
K
Sinsheimer
Janet S
JS
Carr
Andrew
A
Loughlin
John
J
D000368:Aged; D000369:Aged, 80 and over; D019643:Arthroplasty, Replacement; D001224:Aspartic Acid / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D016326:Extracellular Matrix Proteins; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D015207:Osteoarthritis, Hip / Q000453:epidemiology / Q000235:genetics* / Q000601:surgery; D020370:Osteoarthritis, Knee / Q000453:epidemiology / Q000235:genetics* / Q000601:surgery; D011110:Polymorphism, Genetic; D006113:United Kingdom / Q000453:epidemiology
C439889:ASPN protein, human; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D001224:Aspartic Acid