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.
Department of Endocrinology, Odense University Hospital, 5000, Odense C, Denmark. kim.brixen@ouh.fyns-amt.dk
K
K
Brixen
S
S
Beckers
A
A
Peeters
E
E
Piters
W
W
Balemans
T L
TL
Nielsen
K
K
Wraae
L
L
Bathum
C
C
Brasen
C
C
Hagen
M
M
Andersen
W
W
Van Hul
B
B
Abrahamsen
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