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Genetic determinants of trabecular and cortical volumetric bone mineral densities and bone microstructure.

https://arctichealth.org/en/permalink/ahliterature116079
Source
PLoS Genet. 2013;9(2):e1003247
Publication Type
Article
Date
2013
Author
Lavinia Paternoster
Mattias Lorentzon
Terho Lehtimäki
Joel Eriksson
Mika Kähönen
Olli Raitakari
Marika Laaksonen
Harri Sievänen
Jorma Viikari
Leo-Pekka Lyytikäinen
Dan Mellström
Magnus Karlsson
Osten Ljunggren
Elin Grundberg
John P Kemp
Adrian Sayers
Maria Nethander
David M Evans
Liesbeth Vandenput
Jon H Tobias
Claes Ohlsson
Author Affiliation
MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom.
Source
PLoS Genet. 2013;9(2):e1003247
Date
2013
Language
English
Publication Type
Article
Keywords
Absorptiometry, Photon
Alleles
Bone Density - genetics
Bone and Bones - radiography - ultrastructure
Fractures, Bone - genetics - radiography
Genome-Wide Association Study
Humans
Intercellular Signaling Peptides and Proteins - genetics - metabolism
Osteoblasts - metabolism
Osteoporosis - genetics - radiography
RANK Ligand - genetics
Sweden
Tomography, X-Ray Computed
Abstract
Most previous genetic epidemiology studies within the field of osteoporosis have focused on the genetics of the complex trait areal bone mineral density (aBMD), not being able to differentiate genetic determinants of cortical volumetric BMD (vBMD), trabecular vBMD, and bone microstructural traits. The objective of this study was to separately identify genetic determinants of these bone traits as analysed by peripheral quantitative computed tomography (pQCT). Separate GWA meta-analyses for cortical and trabecular vBMDs were performed. The cortical vBMD GWA meta-analysis (n?=?5,878) followed by replication (n?=?1,052) identified genetic variants in four separate loci reaching genome-wide significance (RANKL, rs1021188, p?=?3.6×10?¹4; LOC285735, rs271170, p?=?2.7×10?¹²; OPG, rs7839059, p?=?1.2×10?¹°; and ESR1/C6orf97, rs6909279, p?=?1.1×10??). The trabecular vBMD GWA meta-analysis (n?=?2,500) followed by replication (n?=?1,022) identified one locus reaching genome-wide significance (FMN2/GREM2, rs9287237, p?=?1.9×10??). High-resolution pQCT analyses, giving information about bone microstructure, were available in a subset of the GOOD cohort (n?=?729). rs1021188 was significantly associated with cortical porosity while rs9287237 was significantly associated with trabecular bone fraction. The genetic variant in the FMN2/GREM2 locus was associated with fracture risk in the MrOS Sweden cohort (HR per extra T allele 0.75, 95% confidence interval 0.60-0.93) and GREM2 expression in human osteoblasts. In conclusion, five genetic loci associated with trabecular or cortical vBMD were identified. Two of these (FMN2/GREM2 and LOC285735) are novel bone-related loci, while the other three have previously been reported to be associated with aBMD. The genetic variants associated with cortical and trabecular bone parameters differed, underscoring the complexity of the genetics of bone parameters. We propose that a genetic variant in the RANKL locus influences cortical vBMD, at least partly, via effects on cortical porosity, and that a genetic variant in the FMN2/GREM2 locus influences GREM2 expression in osteoblasts and thereby trabecular number and thickness as well as fracture risk.
Notes
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PubMed ID
23437003 View in PubMed
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Lactase gene c/t(-13910) polymorphism, calcium intake, and pQCT bone traits in Finnish adults.

https://arctichealth.org/en/permalink/ahliterature138798
Source
Calcif Tissue Int. 2011 Feb;88(2):153-61
Publication Type
Article
Date
Feb-2011
Author
Sanna Tolonen
Marika Laaksonen
Vera Mikkilä
Harri Sievänen
Nina Mononen
Leena Räsänen
Jorma Viikari
Olli T Raitakari
Mika Kähönen
Terho J Lehtimäki
Author Affiliation
Division of Nutrition, Department of Food and Environmental Sciences, University of Helsinki, P.O. Box 66, 00014 Helsinki, Finland. sanna.tolonen@helsinki.fi
Source
Calcif Tissue Int. 2011 Feb;88(2):153-61
Date
Feb-2011
Language
English
Publication Type
Article
Keywords
Adult
Bone Density - genetics
Calcium, Dietary - metabolism
Cardiovascular Diseases - genetics
Cohort Studies
European Continental Ancestry Group
Female
Finland
Fractures, Bone - genetics - radiography
Genotype
Humans
Lactase - genetics
Lactose Intolerance - genetics
Male
Polymorphism, Genetic
Risk
Tibia - radiography
Tomography, X-Ray Computed
Abstract
Genetic lactase nonpersistence may influence calcium intake and thereby bone health. We investigated in the Cardiovascular Risk in Young Finn Study whether young adults aged 31-46 years with the C/C(-13910) genotype are more susceptible to reduced bone phenotypes, low-energy fractures, and low calcium intake than subjects with other lactase genotypes. We also analyzed the gene-environment interactions on bone with calcium intake and physical activity. Peripheral quantitative computed tomography bone traits were measured from the distal and shaft sites of the radius and tibia. The total number of those subjects whose nondominant forearm was measured and the lactase genotype was defined was 1551. Information on diet, lifestyle factors, and fractures was collected with questionnaires. The mean intake of calcium was the lowest in men with the C/C(-13910) genotype (P = 0.001). Men with the T/T(-13910) genotype had ~3% higher trabecular density at the distal radius and distal tibia compared to other lactase genotypes (P = 0.03 and 0.02, respectively). In women, we found no evidence of the gene effect at the radius and tibia. No major interactions of the C/T(-13910) polymorphism with calcium intake or physical activity on bone phenotypes were found in either sex. In conclusion, the C/T(-13910) polymorphism was associated with trabecular density at the distal radius and tibia in men. These differences may be due to the differences in calcium intake between the lactase genotypes.
PubMed ID
21136048 View in PubMed
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