title: Genetic predictors of skeletal outcomes in healthy fertile women: the Bonturno study.
abstract: Skeletal traits as height (Ht) or bone mineral density (BMD) are strongly inherited. Low-density lipoprotein receptor-related protein 5 (LRP5) and farnesyl diphosphonate synthase (FDPS) are candidate genes for bone phenotypes. From Bonturno study, we genotyped 570 healthy Caucasian women aged 20 to 50 years (yrs) for LRP5 rs4988321 (A/G) and rs3736228 (C/T) and FDPS rs2297480 (A/C) single nucleotide polymorphisms. Serum C-telopeptide of type I collagen (CTX), osteocalcin (OC), and N-terminal propeptide of type I procollagen (P1NP) were measured in BMD-evaluated subjects at lumbar spine (LS), total hip (TH) and femoral neck (FN) sites. LRP5 rs4988321 locus correlated with FN-BMD (P = 0.0230), while LRP5 rs3736228 genotypes differed in LS-BMD (P = 0.0428). When clustered by age, lower FN-BMD was detected in LRP5 GG (P = 0.030) subjects of 41 to 50 years but not in younger. Both LRP5 GG and CC genotypes showed higher age-adjusted values of OC, CTX and P1NP. Increased CTX values were in LRP5 GGCC subjects than in those having at least one LRP5 A plus T alleles (P = 0.0190). LRP5 CC, GG or GGCC subjects with at least one FDPS C allele showed higher levels of CTX and OC in 31 to 40 yrs or older subjects. In conclusion, LRP5 and FDPS loci age-specifically affect skeletal traits in healthy fertile women.
authors.affiliation: Pediatric Unit, Santa Chiara University Hospital of Pisa, Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Massart
authors.forename: Francesca
authors.initials: F
authors.lastname: Marini
authors.forename: Gerolamo
authors.initials: G
authors.lastname: Bianchi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Minisola
authors.forename: Giovanni
authors.initials: G
authors.lastname: Luisetto
authors.forename: Antonella
authors.initials: A
authors.lastname: Pirazzoli
authors.forename: Sara
authors.initials: S
authors.lastname: Salvi
authors.forename: Dino
authors.initials: D
authors.lastname: Micheli
authors.forename: Mario
authors.initials: M
authors.lastname: Miccoli
authors.forename: Angelo
authors.initials: A
authors.lastname: Baggiani
authors.forename: Francesca
authors.initials: F
authors.lastname: Giusti
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Brandi
mesh_terms: D000328:Adult; D000367:Age Factors; D015519:Bone Density / Q000502:physiology; D001842:Bone and Bones / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D005272:Femur Neck / Q000502:physiology; D005298:Fertility / Q000502:physiology*; D005838:Genotype; D051228:Geranyltranstransferase / Q000235:genetics*; D006801:Humans; D007558:Italy; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics*; D008159:Lumbar Vertebrae / Q000502:physiology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests
chemical_list: C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D051228:Geranyltranstransferase