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.