Low-Density Lipoprotein Receptor-Related Protein 5 Polymorphisms Are Associated with Bone Mineral Density in Greek Postmenopausal Women: An Interaction with Calcium Intake

Abstract The low-density lipoprotein receptor-related protein 5 (LRP5) has been shown to play a significant role in bone biology. This study aimed to assess the association of four common polymorphisms of the LRP5 gene with bone mineral density (BMD) and possible gene×calcium intake interactions in Greek postmenopausal women. For this observational cross-sectional association study, healthy postmenopausal women (N=578) were recruited (between December 2006 and January 2008) and genotyped for four polymorphisms (rs1784235, rs491347, rs4988321, and rs4988330) in the LRP5 gene. Measurements of BMD were performed and detailed medical, dietary, and anthropometric data were recorded. Student t tests and multiple linear regression models were applied after controlling for potential covariates (ie, age, weight, height, and calcium intake). None of the polymorphisms was associated with the presence of osteoporosis, fractures, and hip BMD. All polymorphisms were associated with unadjusted spine BMD, with the exception of rs4988330. Only rs4988321 was associated with adjusted spine BMD, where the presence of the A allele was associated with significantly lower spine BMD compared with the GG genotype ( P =0.002). An interaction of the rs4988321 polymorphism with calcium intake ( P =0.016) was found. The carriers of the A allele demonstrated significantly lower spine BMD compared to GG homozygotes ( P =0.001) only in the lowest calcium intake group (