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

Department of Internal Medicine, Section on Nephrology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1053, USA.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research (Impact Factor: 6.83). 06/2009; 24(10):1719-27. DOI: 10.1359/jbmr.090501
Source: PubMed


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.

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Available from: Donald W Bowden, Jul 29, 2014
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    • "However, this association was not consistent across various ethnic populations. In the recent Diabetes Heart Study [20], bone morphogenetic protein 7 gene polymorphisms were reported to be associated with inverse relationships between vascular calcification and bone mineral density. Bone morphogenetic protein has been proposed to play an inhibitory role in vascular calcification, but its inhibitory effect has not been extensively studied. "
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    • "Possible common etiological factors that may account for the association between the vascular calcification and skeletal decalcification include – BMP-7 and products of lipid oxidation caused by oxidative stress. BMP-7 has been studied extensively by the Hruska laboratory [25]. The Diabetes Heart Study showed that single nucleotide polymorphisms in the BMP-7 gene had statistically significant (and reciprocal) effects on vascular calcification and bone density in a population enriched with diabetes [26]. "
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