Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with peak bone mass in non-sedentary men: results from the Odense androgen study.
OBJECTIVE
To investigate the impact of the Ala1330Val (rs3736228, exon 18) and Val667Met (rs4988321, exon 9) polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene on peak bone mass in young men.


METHODS
The Odense Androgen Study (OAS) is a population-based study comprising 783 Caucasian men aged 20-30 years. Genotyping was performed using real-time polymerase chain reaction (PCR) or fluorescence polarization. Bone mineral density (BMD) measurements were performed using dual-energy X-ray absorptiometry.


RESULTS
The CC, CT, and TT genotypes in Ala1330Val were found in 75.6%, 21.8%, and 2.6% of the participants, respectively. Similarly, the GG, GA, and AA genotypes of Val667Met were found in 89.7%, 9.8%, and 0.5%, respectively. For the Ala1330Val polymorphism, no significant differences between the genotypes were found regarding BMD in the overall study population. However, when analysis was restricted to non-sedentary men (n = 589), a significant association between the number of T-alleles and BMD in the spine and whole body were found. Each copy of the T-allele changed the Z-score of the spine by (median and 95% confidence interval) -0.21 [95% CI: -0.40; -0.03] (p < 0.02). Analysis suggested an association between the AA genotype in the Val667Met polymorphism and increased body height and decreased BMD of the femoral neck; however, no significant gene-dose effect of the A-allele could be demonstrated in the whole population. When the analysis was restricted to non-sedentary subjects, however, each number of A-alleles was associated with a change in Z-score of -0.26 [95% CI: -0.51; -0.01] (p = 0.04). No further significant results emerged with haplotype analysis.


CONCLUSIONS
The Ala1330Val and Val667Met polymorphisms in the LRP5 gene are significantly associated with peak bone mass in physically active men.
Brixen
K
K
Department of Endocrinology, Odense University Hospital, 5000, Odense C, Denmark. kim.brixen@ouh.fyns-amt.dk
Beckers
S
S
Peeters
A
A
Piters
E
E
Balemans
W
W
Nielsen
T L
TL
Wraae
K
K
Bathum
L
L
Brasen
C
C
Hagen
C
C
Andersen
M
M
Van Hul
W
W
Abrahamsen
B
B
D015502:Absorptiometry, Photon; D000409:Alanine / Q000235:genetics; D000728:Androgens / Q000378:metabolism; D015519:Bone Density / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D008019:Life Style; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008297:Male; D008715:Methionine / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D014633:Valine / Q000235:genetics; D044465:White People
D000728:Androgens; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008715:Methionine; D014633:Valine; D000409:Alanine