학술논문

Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men
Document Type
article
Source
Journal of Bone and Mineral Research. 25(2)
Subject
Biological Sciences
Biomedical and Clinical Sciences
Clinical Sciences
Genetics
Clinical Research
Aging
Biotechnology
Osteoporosis
2.1 Biological and endogenous factors
Aetiology
Musculoskeletal
Absorptiometry
Photon
Age Factors
Aged
Aged
80 and over
Bone Density
Femur Neck
Fractures
Bone
Genetic Association Studies
Humans
Male
Polymorphism
Single Nucleotide
Tomography
X-Ray Computed
OSTEOPOROSIS
GENETICS
BMD
MEN
QCT
Osteoporotic Fractures in Men (MrOS) Study Group
Engineering
Medical and Health Sciences
Anatomy & Morphology
Biological sciences
Biomedical and clinical sciences
Language
Abstract
In contrast to conventional dual-energy X-ray absorptiometry, quantitative computed tomography separately measures trabecular and cortical volumetric bone mineral density (vBMD). Little is known about the genetic variants associated with trabecular and cortical vBMD in humans, although both may be important for determining bone strength and osteoporotic risk. In the current analysis, we tested the hypothesis that there are genetic variants associated with trabecular and cortical vBMD at the femoral neck by genotyping 4608 tagging and potentially functional single-nucleotide polymorphisms (SNPs) in 383 bone metabolism candidate genes in 822 Caucasian men aged 65 years or older from the Osteoporotic Fractures in Men Study (MrOS). Promising SNP associations then were tested for replication in an additional 1155 men from the same study. We identified SNPs in five genes (IFNAR2, NFATC1, SMAD1, HOXA, and KLF10) that were robustly associated with cortical vBMD and SNPs in nine genes (APC, ATF2, BMP3, BMP7, FGF18, FLT1, TGFB3, THRB, and RUNX1) that were robustly associated with trabecular vBMD. There was no overlap between genes associated with cortical vBMD and trabecular vBMD. These findings identify novel genetic variants for cortical and trabecular vBMD and raise the possibility that some genetic loci may be unique for each bone compartment.