1 3 J Bone Miner Metab DOI 10.1007/s00774-014-0645-z ORIGINAL ARTICLE Strong effect of SNP rs4988300 of the LRP5 gene on bone phenotype of Caucasian postmenopausal women Péter Horváth · Bernadett Balla · János P. Kósa · Bálint Tóbiás · Balázs Szili · Gyöngyi Kirschner · Gabriella Gyo ˝ri · Karina Kató · Péter Lakatos · István Takács Received: 16 September 2014 / Accepted: 24 November 2014 © The Japanese Society for Bone and Mineral Research and Springer Japan 2015 interaction between two SNPs of LRP5 (rs4988300 and rs634008, p = 0.009) which was lost after Bonferroni cor- rection. We could firmly demonstrate a significant associa- tion between rs4988300 of the LRP5 gene and bone den- sity of the hip on the largest homogeneous postmenopausal study group analyzed to date. Our finding corroborates the relationship between LRP5 genotype and bone phenotype in postmenopausal women, however, the complete mecha- nism of this relationship requires further investigations. Keywords Osteoporosis · Wnt signaling · Bone metabolism · Genetic epidemiology Introduction Osteoporosis is a complex disease with a strong genetic background [1]. The genetic effects are mediated through a wide variety of genes [2]. Genetic effects were observed in all phases of bone metabolism, in bone formation as well as in bone resorption. The receptor activator of nuclear fac- tor kappa-B (RANK)/receptor activator of the nuclear fac- tor kappa-B ligand (RANKL) pathway is a crucial element in bone resorption [3]. Genome-wide association studies (GWAS) studies showed that single nucleotide polymor- phisms (SNPs) in the genes of the RANK/RANKL pathway were associated with bone mass and fracture risks [4, 5]. The Wnt pathway plays an important role in bone metabolism, especially bone formation, and its altera- tions are associated with osteoporosis [6–11]. Members of this pathway are in close relationship with bone develop- ment and bone density. The most investigated factor of the Wnt pathway in osteoblast differentiation is the LRP5/6 [12]. The gain of function mutations of LRP5/6 result in high bone mass or osteopetrosis, and the loss of function Abstract The purpose of this study was to identify rela- tionships between single nucleotide polymorphisms (SNPs) in the genes of the Wnt pathway and bone mineral density (BMD) of postmenopausal women. We chose this pathway due to its importance in bone metabolism that was under- lined in several studies. DNA samples of 932 Hungarian postmenopausal women were studied. First, their BMD values at different sites (spine, total hip) were measured, using a Lunar Prodigy DXA scanner. Thereafter, T-score values and the patients’ body mass indices (BMIs) were calculated, while information about the fracture history of the sample population was also collected. We genotyped nine SNPs of the following three genes: LRP5, GPR177, and SP7, using a Sequenom MassARRAY Analyzer 4 instrument. The genomic DNA samples used for genotyp- ing were extracted from the buccal mucosa of the subjects. Statistical analyses were carried out using the SPSS 21 and R package. The results of this analysis showed a sig- nificant association between SNP rs4988300 of the LRP5 gene and total hip BMD values. We could not reveal any associations between the markers of GPR177, SP7, and bone phenotypes. We found no effect of these genotypes on fracture risk. We could demonstrate a significant gene–gene Electronic supplementary material The online version of this article (doi:10.1007/s00774-014-0645-z) contains supplementary material, which is available to authorized users. P. Horváth (*) · B. Balla · J. P. Kósa · B. Tóbiás · B. Szili · G. Kirschner · K. Kató · P. Lakatos · I. Takács 1st Department of Internal Medicine, Semmelweis University, Korányi Sándor u. 2/a, Budapest 1089, Hungary e-mail: horv.peter88@gmail.com G. Gyo ˝ri Department of Radiology, Semmelweis University, Budapest, Hungary