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.


Genetic Variants Associated with Susceptibility to Knee Osteoarthritis: The Johnston County Osteoarthritis Project.

Wu3,  Xiaodong, Kondragunta4,  Venkateswarlu, Renner2,  Jordan B., Duff5,  Gordon W., Kornman4,  Kenneth S., Jordan1,  Joanne M.

Chapel Hill, NC
Department of Radiology and Thurston Arthritis Research Center, University of North Carolina at Chapel Hill
Interleukin Genetics, Inc., Waltham, MA
Interleukin Genetics, Inc.
School of Medicine, University of Sheffield

Purpose:

Factors that differentiate individuals who develop osteoarthritis (OA) from those who do not may be valuable in developing prevention strategies. Although several genetic variants have been associated with susceptibility to OA, most have not been replicated in adequately sized cohorts. We therefore sought to validate genetic variants predictive of OA susceptibility in a Caucasian patient sample in the United States, in a population-based study.

Method:

Caucasian participants (N=1,173; 38% men; mean age=60 years) in the Johnston County OA Project were examined for susceptibility to radiographic knee OA in a cross-sectional analysis. Anterior-posterior standing knee radiographs were obtained with footmat positioning and read by a single musculoskeletal radiologist for Kellgren-Lawrence grade (K-L, 0–4). OA cases were defined as having KL>=2 in at least one knee. Non-OA controls were defined as having KL=0 in both knees. Genotypes of 37 single nucleotide polymorphisms (SNPs) in 16 genes, including gene variants previously shown to be associated with OA and variants in genes that are functionally implicated in OA, such as the proinflammatory IL-1 gene family, were determined using the single-nucleotide primer extension method. Logistic regression with adjustment for age, gender and body mass index was used to determine associations between gene polymorphisms and susceptibility to radiographic knee OA. Since this was not an exploratory analysis, we analyzed the data without correction for multiple comparisons, but also report the results of a permutation test for multiple comparisons. An association was considered a positive validation if the p-value after adjustment for age, gender and BMI <0.05 for the risk allele, genotype or haplotype previously reported to be associated with OA.

Results:

Out of 16 genes tested, 6 were significantly associated with susceptibility to radiographic knee OA. These included ABCG2, GDF5, IL1R1, IL1RN, IL6 and VDR genes (table 1). VDR rs731236 also showed significance after correction for multiple comparisons.

Table 1. Genetic variants associated with susceptibility to radiographic knee OA.

GeneSNPAllele/genotypeOR95% CI (L)95% CI (U)P
GDF5rs143383C/C0.570.360.910.018
VDRrs1544410T/*1.511.072.130.020
IL6rs1800797A1.381.091.740.008
ABCG2rs2231142A/*0.640.420.970.036
IL1R1rs2287047T0.740.560.970.029
IL1RNrs380092T/T0.560.330.960.034
VDRrs731236C/*1.691.192.390.003

Conclusion:

This study validated several genetic markers for association with susceptibility to radiographic knee OA in a population-based study of Caucasians.

To cite this abstract, please use the following information:
Wu, Xiaodong, Kondragunta, Venkateswarlu, Renner, Jordan B., Duff, Gordon W., Kornman, Kenneth S., Jordan, Joanne M.; Genetic Variants Associated with Susceptibility to Knee Osteoarthritis: The Johnston County Osteoarthritis Project. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :831
DOI: 10.1002/art.28599

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