Bone Morphogenetic Protein 7 (BMP7) Gene Polymorphisms Are Associated With Inverse Relationships Between Vascular Calcification and BMD: The Diabetes Heart Study

• Published in: Journal of bone and mineral research Vol. 24; no. 10; pp. 1719 - 1727
• Main Authors: Freedman, Barry I, Bowden, Donald W, Ziegler, Julie T, Langefeld, Carl D, Lehtinen, Allison B, Rudock, Megan E, Lenchik, Leon, Hruska, Keith A, Register, Thomas C, Carr, J Jeffrey
• Format: Journal Article
• Language: English
• Published: Washington, DC John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR) 01.10.2009; Wiley; Amer Soc Bone & Mineral Res
• Subjects: Biological and medical sciences; Blood Vessels - pathology; Blood Vessels - physiopathology; BMD; BMP2; BMP4; BMP7; Bone Density - genetics; Bone Density - physiology; Bone Morphogenetic Protein 2 - genetics; Bone Morphogenetic Protein 4 - genetics; Bone Morphogenetic Protein 7 - genetics; calcified atherosclerotic plaque; Calcinosis - complications; Calcinosis - genetics; Calcinosis - physiopathology; Demography; diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - physiopathology; European Continental Ancestry Group - genetics; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Heart - physiopathology; Humans; Linkage Disequilibrium - genetics; Male; Middle Aged; Original; osteoporosis; Polymorphism, Single Nucleotide - genetics; Principal Component Analysis; Skeleton and joints; Vertebrates: osteoarticular system, musculoskeletal system; Endocrinopathy; Heart; calcified atherosclerotic plaque; Diabetes mellitus; Diseases of the osteoarticular system; Cardiovascular disease; BMP7; Vascular disease; Osteoarticular system; BMP4; Osteoporosis; Vertebrata; BMP2; Mammalia; Bone morphogenetic protein; Gene; Atherosclerotic plaque; Atherosclerosis; Calcification; BMD; Circulatory system; Polymorphism
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.090501

Inverse relationships have been observed between BMD and vascular calcification (VC), suggesting an underlying metabolic pathway linking these processes. Bone morphogenetic proteins (BMPs) are potential candidate genes that may mediate this relationship. Four single nucleotide polymorphisms (SNPs) in the BMP2 gene, 2 SNPs in BMP4, and 16 SNPs in BMP7 were tested for association with measures of VC using CT (coronary and carotid arteries, abdominal aorta), and BMD was measured using DXA (lumbar spine, hip, and distal radius) and quantitative CT (QCT; thoracic and lumbar spine) in 920 European Americans from 374 Diabetes Heart Study families: 762 with type 2 diabetes. Variance components quantitative trait locus association analysis was computed using SOLAR software, and a bivariate principal component analysis (PCA) assessed for genetic relationships between BMD and VC. Association was observed between several measures of BMD and BMP7 rs17404303 (thoracic spine QCT p = 0.03; lumbar spine QCT p = 0.02; hip DXA p = 0.06, dominant models). In addition, 6 of 16 BMP7 SNPs showed significant and opposing effects on the bivariate PCA for VC and BMD (two‐sided exact test, p = 0.0143). Polymorphisms in BMP7 are associated with inverse relationships between bone mineralization and VC in the coronary, carotid, and abdominal aorta in a diabetes‐enriched cohort of European Americans.