LRP5 gene polymorphism and cortical bone.
OBJECTIVE
There is evidence that distinct genetic polymorphisms of LRP5 are associated with low Bone Mineral Density (BMD) and the risk of fracture. However, relationships between LRP5 polymorphisms and micro- and macro architectural bone characteristics assessed by pQCT have not been studied. The aim of the present study was to investigate the association of Ala1330Val and Val667Met polymorphisms in LRP5 gene with volumetric BMD (vBMD) and macro-architectural bone parameters in a population-based sample of men and women.


METHODS
We studied 959 participants of the InCHIANTI study (451 men and 508 women, age range: 21-94 yrs). Trabecular vBMD (vBMDt, mg/cm3), cortical vBMD (vBMDc, mg/cm3), cortical bone area (CBA, mm2) and cortical thickness (Ct.Th, mm) at the level of the tibia were assessed by peripheral quantitative computed tomography (pQCT). Ala1330Val and Val667Met genotypes were determined on genomic DNA by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).


RESULTS
In age-adjusted analyses both LRP 1330-valine and LRP 667-metionin variants were associated with lower vBMDt in men (p<0.05), and lower vBMDt (p<0.05), Ct.Th (p<0.05) and CBA (p<0.05) in women. After adjusting for multiple confounders, only the association of LRP5 1330-valine and 667-metionin with CBA remained statistically significant (p=0.04 and p=0.01, respectively) in women.


CONCLUSIONS
These findings suggest that both Ala1330Val and Val667Met LRP5 polymorphisms may affect the determination of geometric bone parameters in women.
Tuscany Regional Health Agency, Italy. flauretani@ao.pr.it
Fulvio
F
Lauretani
Chiara
C
Cepollaro
Stefania
S
Bandinelli
Antonio
A
Cherubini
Alessia
A
Gozzini
Laura
L
Masi
Alberto
A
Falchetti
Francesca
F
Del Monte
Silvia
S
Carbonell-Sala
Francesca
F
Marini
Annalisa
A
Tanini
Anna Maria
AM
Corsi
Gian Paolo
GP
Ceda
Maria Luisa
ML
Brandi
Luigi
L
Ferrucci
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D015519:Bone Density / Q000235:genetics*; D001842:Bone and Bones / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D007558:Italy; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D020641:Polymorphism, Single Nucleotide; D014057:Tomography, X-Ray Computed; D055815:Young Adult
D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5