Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Association of FRZB Variants with Hip Shape and Radiographic Hip Osteoarthritis: Preliminary Results.

Baker-LePain4,  Julie, Luker2,  Kali, Lynch4,  John A., Parimi1,  Neeta, Nevitt3,  Michael C., Corr6,  Mary, Lane5,  Nancy E.

California Pacific Medical Center
Stanford
UCSF, San Francisco, CA
UCSF
Univ of California at Davis, Hillsborough, CA
Univ of California-San Diego, La Jolla, CA

Background:

Single nucleotide polymorphisms (SNPs) in the FRZB gene, which encodes the Wnt antagonist secreted frizzled-related protein 3 (sFRP3), are significant predictors of radiographic hip osteoarthritis (RHOA) (Lane, et al., A&R 2006). In addition to FRZB, another important predictor of incident RHOA is hip shape (Lynch, et al., O&C 2009). Since the Wnt pathway is a key regulator of joint development, we examined whether FRZB variants are associated with hip shape and to what extent the relationship between joint shape and RHOA is affected FRZB.

Methods:

We performed a nested case-control study within the Study of Osteoporotic Fractures (SOF). Subjects were Caucasian women aged >= 65 years with supine pelvic radiographs at baseline visit and at follow-up (mean 8.3 years). RHOA was scored radiographically using a modified summary grade (scale 0–4). Cases (n = 451) were defined as subjects with no baseline radiographic hip OA (RHOA) in either hip at baseline and incident RHOA (summary grade >= 2) at follow-up. Controls (n = 601) had no RHOA at either time point. We determined hip shape at 2 sites: the proximal femur by active shape modeling (ASM) (Lynch et al., O&C 2009) and the acetabulum by the center-edge angle and acetabular depth. Genotyping for the rs288326 SNP of FRZB was performed using allele-specific polymerase chain reaction (PCR). Linear regression was used to determine the association of hip shape parameters with the presence of the rs288326 FRZB SNP.

Results:

In preliminary analsis, we found that among controls, proximal femur shape (Mode 2 from ASM analysis) was associated with the rs288326 FRZB SNP (coefficient -0.18, 95% CI -0.35 to 0.03, p = 0.05) after adjustment for age and femoral neck BMD. The presence of the rs288326 allele modified the association between proximal femur shape Mode 2 and RHOA (p-value for trend = 0.01, see Figure). Similarly, in preliminary results (n = 202 cases and n = 512 controls), the rs288326 allele modified the association between acetabular depth/center edge angle and RHOA (p-value for trend < 0.001).

Figure. Quartiles of increasing proximal femur ASM Mode 2 or decreasing acetabular depth were created using control populations, and the association between the rs288326 FRZB allele and incident RHOA was examined in each quartile using logistic regression. Odds ratio with 95% CI is shown, together with p-value for test of linear trend. The referent group was subjects without the rs288326 FRZB allele.

Conclusions:

Hip shape is known to be an important predictor of incident OA. In this preliminary analysis, we find that variants in the FRZB gene, a component of the Wnt pathway, may be involved in moderating the relationship between hip shape and OA. We hypothesize that Wnt pathway components play a key role in determination of joint shape, which in turn may predispose to development of osteoarthritis in a conducive architectural setting.

To cite this abstract, please use the following information:
Baker-LePain, Julie, Luker, Kali, Lynch, John A., Parimi, Neeta, Nevitt, Michael C., Corr, Mary, et al; Association of FRZB Variants with Hip Shape and Radiographic Hip Osteoarthritis: Preliminary Results. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :624
DOI: 10.1002/art.28392

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