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The A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene (LRP5) associates with low peak bone mass in young healthy men.

https://arctichealth.org/en/permalink/ahliterature165637
Source
Bone. 2007 Apr;40(4):1006-12
Publication Type
Article
Date
Apr-2007
Author
Anne Saarinen
Ville-Valtteri Välimäki
Matti J Välimäki
Eliisa Löyttyniemi
Kirsi Auro
Piia Uusen
Mairi Kuris
Anna-Elina Lehesjoki
Outi Mäkitie
Author Affiliation
Folkhälsan Institute of Genetics and Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
Source
Bone. 2007 Apr;40(4):1006-12
Date
Apr-2007
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Alleles
Bone Density - genetics
Calcifediol - blood
Finland
Fractures, Bone - etiology - genetics
Gene Frequency
Humans
LDL-Receptor Related Proteins - genetics
Low Density Lipoprotein Receptor-Related Protein-5
Male
Military Personnel
Osteoporosis - etiology - genetics
Parathyroid Hormone - blood
Polymorphism, Single Nucleotide
Risk factors
Abstract
Polymorphisms in the gene coding for low-density lipoprotein receptor-related protein 5 (LRP5) contribute to variation in bone mass in the general population. Whether this is due to influence on bone mass acquisition or on bone loss thereafter has not been established.
We studied the association of LRP5 polymorphisms with peak bone mass in young men. The study included 235 Finnish men, aged 18.3 to 20.6 years. Lifestyle factors and fracture history were recorded. Bone mineral content (BMC), density (BMD) and scan area were measured for the lumbar spine and proximal femur by dual energy X-ray absorptiometry (DXA). Blood and urine were collected for determination of bone turnover markers, serum 25-OHD and PTH. Genomic DNA was extracted from peripheral blood for genetic analysis of LRP5. Ten single nucleotide polymorphisms in LRP5 were analyzed and correlated with bone parameters.
Only the A1330V polymorphism of LRP5 significantly associated with bone parameters. In comparison with subjects with the AlaAla genotype (n=215), those with AlaVal genotype (n=20) had lower femoral neck BMC (P=0.029) and BMD (P=0.012), trochanter BMC (P=0.0067) and BMD (P=0.015), and total hip BMC (P=0.0044) and BMD (P=0.0089). Fracture history was similar for the genotypes.
The polymorphic valine variant at position 1330 of LRP5 was significantly associated with reduced BMC and BMD values in healthy young Finnish men. The results provide evidence for the crucial role of LRP5 in peak bone mass acquisition.
PubMed ID
17223614 View in PubMed
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Variable number of tandem repeats polymorphism in parathyroid hormone-related protein as predictor of peak bone mass in young healthy Finnish males.

https://arctichealth.org/en/permalink/ahliterature157624
Source
Eur J Endocrinol. 2008 May;158(5):755-64
Publication Type
Article
Date
May-2008
Author
Ajay Gupta
Ville-Valtteri Välimäki
Matti J Välimäki
Eliisa Löyttyniemi
Marilyn Richard
Prasanna L Bukka
David Goltzman
Andrew C Karaplis
Author Affiliation
Osta Biotechnologies Inc., Pointe Claire, Québec, H9A 3H2 Canada.
Source
Eur J Endocrinol. 2008 May;158(5):755-64
Date
May-2008
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Alleles
Animals
Base Sequence
Bone Density - genetics
COS Cells
Cercopithecus aethiops
Finland
Genetic Variation
Humans
Lumbar Vertebrae - ultrasonography
Male
Molecular Sequence Data
Osteoblasts - cytology - physiology
Osteoporosis - epidemiology - genetics
Parathyroid Hormone-Related Protein - genetics
Polymorphism, Genetic
Predictive value of tests
Risk factors
Tandem Repeat Sequences
Abstract
Mice with osteoblast-specific deletion of parathyroid hormone-related protein (PTHrP) exhibit impaired recruitment and increased apoptosis of osteogenic cells resulting in decreased bone formation and premature osteoporosis. The PTHrP levels within the bone microenvironment are therefore critical in influencing bone mass acquisition. Whether this is applicable in humans has not been established. Here, we studied the association of a variable number of tandem repeats (VNTR) polymorphism in PTHrP with peak bone mass.
Enrolled in the study were 234 young Finnish males, with median age of 19.6 years (range 18.3-20.6 years). Lifestyle factors, serum bone markers, osteodensitometric measurements (lumbar spine and hip) and calcaneal quantitative ultrasound readings were obtained. The PTHrP VNTR length was determined by the PCR amplification of genomic DNA extracted from peripheral blood and correlated to bone parameters by the multiple regression models.
The presence of at least one 252 bp allele was associated with increased lumbar spine bone mineral density (BMD; P
PubMed ID
18426836 View in PubMed
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Vitamin D status as a determinant of peak bone mass in young Finnish men.

https://arctichealth.org/en/permalink/ahliterature182083
Source
J Clin Endocrinol Metab. 2004 Jan;89(1):76-80
Publication Type
Article
Date
Jan-2004
Author
Ville-Valtteri Välimäki
Henrik Alfthan
Eero Lehmuskallio
Eliisa Löyttyniemi
Timo Sahi
Ulf-Håkan Stenman
Harri Suominen
Matti J Välimäki
Author Affiliation
Division of Endocrinology, Department of Medicine, Helsinki University Central Hospital, FIN-00290 Helsinki, Finland.
Source
J Clin Endocrinol Metab. 2004 Jan;89(1):76-80
Date
Jan-2004
Language
English
Publication Type
Article
Keywords
Absorptiometry, Photon
Adolescent
Adult
Body Weight
Bone Density
Calcifediol - blood
Cross-Sectional Studies
Exercise
Femur
Femur Neck
Finland
Humans
Life Style
Lumbar Vertebrae
Male
Military Personnel
Nutritional Status
Parathyroid Hormone - blood
Prospective Studies
Retrospective Studies
Seasons
Vitamin D Deficiency - epidemiology
Abstract
Severe vitamin D deficiency causes rickets, but scarce data are available about the extent to which vitamin D status determines the development of the peak bone mass in young adults. Our aim was to evaluate the prevalence of vitamin D deficiency [serum 25-hydroxyvitamin D (25-OHD) less than the lower limit of the reference range of 20-105 nmol/liter] and the relationship between vitamin D status and peak bone mass among young Finnish men. A cross-sectional study of determinants of peak bone mass with data on lifestyle factors collected retrospectively was performed in 220 young men, aged 18.3-20.6 yr. One hundred and seventy men were recruits of the Finnish Army, and 50 were men of similar age who had postponed their military service for reasons not related to health. Bone mineral content, bone mineral density, and scan area were measured in lumbar spine and upper femur by dual energy x-ray absorptiometry. Serum 25-OHD concentrations were followed prospectively for 1 yr. In July 2000, only 0.9% of the men had vitamin D deficiency, but 6 months later, in the winter, the respective percentage was 38.9%. After adjusting for age, height, weight, exercise, smoking, calcium, and alcohol intake, there existed a positive correlation between serum 25-OHD and bone mineral content at lumbar spine (P = 0.057), femoral neck (P = 0.041), trochanter (P = 0.010), and total hip (P = 0.025). The correlation coefficients for the bone mineral densities at the four measurement sites were 0.035, 0.061, 0.056, and 0.068, respectively. No correlation was found to scan area. We conclude that vitamin D deficiency is very common in Finnish young men in the winter, and it may have detrimental effects on the acquisition of maximal peak bone mass. As in Finland vitamin D supplementation to infants is now stopped at the age of 3 yr, it can be asked whether at our latitude it should be continued from that age onward, not for the prevention of rickets, but as prophylaxis for osteoporosis.
PubMed ID
14715830 View in PubMed
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