title: Bone morphogenetic protein 7 (BMP7) gene polymorphisms are associated with inverse relationships between vascular calcification and BMD: the Diabetes Heart Study.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Section on Nephrology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1053, USA. bfreedma@wfubmc.edu
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Julie T
authors.initials: JT
authors.lastname: Ziegler
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Allison B
authors.initials: AB
authors.lastname: Lehtinen
authors.forename: Megan E
authors.initials: ME
authors.lastname: Rudock
authors.forename: Leon
authors.initials: L
authors.lastname: Lenchik
authors.forename: Keith A
authors.initials: KA
authors.lastname: Hruska
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Register
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
mesh_terms: D001808:Blood Vessels / Q000473:pathology* / Q000503:physiopathology; D015519:Bone Density / Q000235:genetics* / Q000502:physiology; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics*; D002114:Calcinosis / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D003710:Demography; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D044465:White People / Q000235:genetics
chemical_list: C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7