title: Strong effect of SNP rs4988300 of the LRP5 gene on bone phenotype of Caucasian postmenopausal women.
abstract: The purpose of this study was to identify relationships 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 underlined 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 genotyping 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 significant 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 interaction between two SNPs of LRP5 (rs4988300 and rs634008, p = 0.009) which was lost after Bonferroni correction. We could firmly demonstrate a significant association between rs4988300 of the LRP5 gene and bone density 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 mechanism of this relationship requires further investigations.
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi Sándor u. 2/a, Budapest, 1089, Hungary. horv.peter88@gmail.com.
authors.forename: Péter
authors.initials: P
authors.lastname: Horváth
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi Sándor u. 2/a, Budapest, 1089, Hungary.
authors.forename: Bernadett
authors.initials: B
authors.lastname: Balla
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi Sándor u. 2/a, Budapest, 1089, Hungary.
authors.forename: János P
authors.initials: JP
authors.lastname: Kósa
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi Sándor u. 2/a, Budapest, 1089, Hungary.
authors.forename: Bálint
authors.initials: B
authors.lastname: Tóbiás
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi Sándor u. 2/a, Budapest, 1089, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Szili
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi Sándor u. 2/a, Budapest, 1089, Hungary.
authors.forename: Gyöngyi
authors.initials: G
authors.lastname: Kirschner
authors.affiliation: Department of Radiology, Semmelweis University, Budapest, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Győri
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi Sándor u. 2/a, Budapest, 1089, Hungary.
authors.forename: Karina
authors.initials: K
authors.lastname: Kató
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi Sándor u. 2/a, Budapest, 1089, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Lakatos
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi Sándor u. 2/a, Budapest, 1089, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Takács
mesh_terms: D000368:Aged; D015519:Bone Density / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D015810:Linkage Disequilibrium; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics*; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017698:Postmenopause / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D043562:Receptors, G-Protein-Coupled; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; C549111:WLS protein, human
keywords: Bone metabolism; Genetic epidemiology; Osteoporosis; Wnt signaling