|Booth, Sarah l.|
|Crosier, Michael d.|
|Ordovas, Jose m.|
|Felson, David t.|
Submitted to: Journal of Rheumatology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 4/26/2011
Publication Date: 7/1/2011
Citation: Misra, D., Booth, S., Crosier, M., Ordovas, J., Felson, D., Neogi, T. 2011. Matrix Gla Protein polymorphism, but not concentrations, is associated with radiographic hand osteoarthritis. Journal of Rheumatology. DOI: 10.3899/jrheum.100985. Interpretive Summary: Factors associated with abnormal mineralization in osteoarthritis are not well understood. Matrix Gla Protein is a protein that requires vitamin K to function as an inhibitor of abnormal calcification. Genetic polymorphisms of Matrix Gla Protein have been associated clinically with conditions of abnormal calcification. We evaluated the relationship of genetic polymorphisms of Matrix Gla Protein to the presence of osteoarthritis in hand joints. In a three-year randomized trial assessing the effect of vitamin K supplementation on vascular calcification and bone loss among community-dwelling elders, we studied participants who were DNA genotyped for Matrix Gla Protein genetic polymorphisms, and who had hand x-rays at the end of the three year study. Hand osteoarthritis in one or more joints was present in 71% of the 376 men and women, who were an average age of 74 years. Those individuals who had minor form of a gene that codes for Matrix Gla Protein had less hand osteoarthritis compared with those having the major form of this gene. In conclusion, there may be an association between hand osteoarthritis and genetic polymorphisms of Matrix Gla Protein. Further studies are needed to replicate and elucidate potential mechanisms underlying these observed associations.
Technical Abstract: Objective. Factors associated with mineralization and osteophyte formation in osteoarthritis (OA) are incompletely understood. Genetic polymorphisms of matrix Gla protein (MGP), a mineralization inhibitor, have been associated clinically with conditions of abnormal calcification. We therefore evaluated the relationship of MGP concentrations and polymorphisms at the MGP locus to hand OA. Methods. Ours was an ancillary study to a 3-year randomized trial assessing the effect of vitamin K supplementation on vascular calcification and bone loss among community-dwelling elders. We studied participants who had serum MGP concentration measured and DNA genotyped for 3 MGP genetic polymorphisms (rs1800802, rs1800801, and rs4236), and who had hand radiographs. We evaluated the cross-sectional associations of serum MGP and the 3 MGP genetic polymorphisms, respectively, with radiographic hand OA using logistic regression with generalized estimating equations, adjusting for potential confounders. Results. Radiographic hand OA in = 1 joint was present in 71% of the 376 participants (mean age 74 years, mean body mass index 28 kg/m2, 59% women). No significant association between serum MGP concentrations and radiographic hand OA was found [adjusted OR 1.0 (ref), 1.40, 1.21, and 1.21 for quartiles 1-4, respectively]. Homozygosity of the rs1800802 minor allele was associated with 0.56 times lower prevalence of hand OA compared with having = 1 major allele at this locus (95% CI 0.32-0.99, p = 0.046). Conclusion. There may be an association between hand OA and genetic polymorphism at the MGP locus that is not reflected by total MGP serum concentrations. Further studies are warranted to replicate and elucidate potential mechanisms underlying these observed associations.