Abstract
A role for matrix proteins has previously been proposed in the pathogenesis of arterial calcification in the setting of atherosclerosis, and a link has been suggested between osteoporosis and arterial calcification. Our aim has been to investigate whether matrix Gla protein (MGP) T-138C, osteopontin (SPP1) T-443C, and Asp94Asp single nucleotide polymorphisms are associated with the development of arterial calcification and bone density. The individual effects of the MGP and SPP1 polymorphisms with coronary calcification are weak and not statistically significant. Bone mineral density differences at both the hip and spine do not vary statistically by genotype for any of the polymorphisms studied. Given the significant role of both MGP and SPP1 in arteriosclerosis, further research in higher risk, older populations are needed to determine fully the way in which MGP and SPP1 polymorphisms are associated with disease.
References
Canfield AE, Farrington C, Dziobon MD, Boot-Handford RP, Heagerty AM, Kumar SN, Roberts IS (2002) The involvement of matrix glycoproteins in vascular calcification and fibrosis: an immunohistochemical study. J Pathol 196:228–234
Carr JJ, Nelson JC, Wong NA, McNitt-Gray M, Arad Y, Jacobs DR Jr, Sidney S, Bild DE, Williams OD, Detrano R (2005) Calcified coronary artery plaque measurement with cardiac CT in population-based studies: the standardized protocol of the Multi-Ethnic study of atherosclerosis (MESA) and Coronary Artery Risk Development in Young Adults (CARDIA) study. Radiology 234:35--43
Dhore CR, Cleutjens JP, Lutgens E, Cleutjens KB, Geusens PP, Kitslaar PJ, Tordoir JH, Spronk HM, Vermeer C, Daemen MJ (2001) Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol 21:1998–2003
Doherty TM, Fitzpatrick LA, Inoue D, Qiao JH, Fishbein MC, Detrano RC, Shah PK, Rajavashisth TB (2004) Molecular, endocrine, and genetic mechanisms of arterial calcification. Endocr Rev 25:629–672
Friedman GD, Cutter GR, Donahue RP, Hughes GH, Hulley SB, Jacobs DR Jr, Liu K, Savage PJ (1988) CARDIA: study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol 41:1105–1116
Giacopelli F, Marciano R, Pistorio A, Catarsi P, Canini S, Karsenty G, Ravazzolo R (2004) Polymorphisms in the osteopontin promoter affect its transcriptional activity. Physiol Genomics 20:87–96
Jono S, Ikari Y, Vermeer C, Dissel P, Hasegawa K, Shioi A, Taniwaki H, Kizu A, Nishizawa Y, Saito S (2004) Matrix Gla protein is associated with coronary artery calcification as assessed by electron-beam computed tomography. Thromb Haemost 91:790–794
Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G (1997) Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 386:78–81
Speer MY, McKee MD, Guldberg RE, Liaw L, Yang HY, Tung E, Karsenty G, Giachelli CM (2002) Inactivation of the osteopontin gene enhances vascular calcification of matrix Gla protein-deficient mice: evidence for osteopontin as an inducible inhibitor of vascular calcification in vivo. J Exp Med 196:1047–1055
Taylor BC (2004) Genetic factors in bone density, fracture risk and arterial calcification: an epidemiological investigation using the study of osteoporotic fractures (SOF) and the coronary artery risk development in young adults (CARDIA) study. Dissertation Abstracts International 65:2899B (UMI no. AAT 3137149)
Acknowledgements
This work was partially supported by contracts N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, and N01-HC-95095 from the National Heart, Lung and Blood Institute. T.M.D. was supported by a grant from Philip Morris USA.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Taylor, B.C., Schreiner, P.J., Doherty, T.M. et al. Matrix Gla protein and osteopontin genetic associations with coronary artery calcification and bone density: the CARDIA study. Hum Genet 116, 525–528 (2005). https://doi.org/10.1007/s00439-005-1258-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00439-005-1258-3