title: LRP5 gene polymorphisms and idiopathic osteoporosis in men.
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.
authors.affiliation: Service of Bone Diseases, Department of Rehabilitation and Geriatrics, Geneva University Hospital, Geneva, Switzerland.
authors.forename: S L
authors.initials: SL
authors.lastname: Ferrari
authors.forename: S
authors.initials: S
authors.lastname: Deutsch
authors.forename: C
authors.initials: C
authors.lastname: Baudoin
authors.forename: M
authors.initials: M
authors.lastname: Cohen-Solal
authors.forename: A
authors.initials: A
authors.lastname: Ostertag
authors.forename: S E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: R
authors.initials: R
authors.lastname: Rizzoli
authors.forename: M C
authors.initials: MC
authors.lastname: de Vernejoul
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010024:Osteoporosis / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5