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LRP5 gene polymorphisms and idiopathic osteoporosis in men

Deutsch, Samuel
Baudoin, C.
Cohen-Solal, M.
Ostertag, A.
de Vernejoul, M. C.
Published in Bone. 2005, vol. 37, no. 6, p. 770-775
Abstract Mutations in the low-density lipoprotein receptor-related protein 5 gene (LRP5) have demonstrated the role of LRP5 in bone mass acquisition. LRP5 variants were recently reported to contribute to the population-based variance in vertebral bone mass and size in males. To investigate whether LRP5 variants are implicated in idiopathic male osteoporosis, we studied 78 men with low BMD (<2.5 T score or < -2 Z score) aged less than 70 years (mean +/- SD: 50 +/- 16 years) in whom secondary causes of osteoporosis had been excluded and 86 controls (51 +/- 10 years). Genotypes and haplotypes were based on LRP5 missense substitutions in exons 9 (c.2047G > A, p.V667M) and 18 (c.4037C > T, p.A1330V), and their association with osteoporosis evaluated after adjustment for multiple clinical and environmental variables using logistic regression. The presence of osteoporosis was significantly associated with LRP5 haplotypes (P = 0.0036) independent of age (P = 0.006), weight (P = 0.004), calcium intake (P = 0.002), alcohol (P = 0.005) and tobacco (P = 0.004) consumption. Accordingly, the odds ratio for osteoporosis was 3.78 (95% CI 1.27-11.26, P < 0.001) in male carriers of haplotype 3 (c.2047A-4037T, n = 20 cases and 12 controls) versus homozygous carriers of haplotype 1 (c.2047G-4037C, n = 42 cases and 61 controls). In conclusion, these data indicate beyond a significant role for environmental factors, an association between LRP5 variants and idiopathic osteoporosis in males, pointing to a role of LRP5 in this disease.
Keywords AdultAgedAmino Acid SubstitutionCase-Control StudiesGenetic Predisposition to DiseaseHaplotypesHumansLDL-Receptor Related Proteins/ geneticsMaleMiddle AgedMutation, MissenseOsteoporosis/ geneticsPolymorphism, Genetic
PMID: 16168727
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FERRARI, Serge Livio et al. LRP5 gene polymorphisms and idiopathic osteoporosis in men. In: Bone, 2005, vol. 37, n° 6, p. 770-775. doi: 10.1016/j.bone.2005.06.017 https://archive-ouverte.unige.ch/unige:8743

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Deposited on : 2010-07-12

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