Strong effect of SNP rs4988300 of the LRP5 gene on bone phenotype of Caucasian postmenopausal women

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• 作者：Péter Horváth ; Bernadett Balla ; János P. Kósa…
• 关键词：Osteoporosis ; Wnt signaling ; Bone metabolism ; Genetic epidemiology
• 刊名：Journal of Bone and Mineral Metabolism
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：34
• 期：1
• 页码：79-85
• 全文大小：480 KB
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• 作者单位：Péter Horváth (1)
  Bernadett Balla (1)
  János P. Kósa (1)
  Bálint Tóbiás (1)
  Balázs Szili (1)
  Gyöngyi Kirschner (1)
  Gabriella Győri (2)
  Karina Kató (1)
  Péter Lakatos (1)
  István Takács (1)
  
  1. 1st Department of Internal Medicine, Semmelweis University, Korányi Sándor u. 2/a, Budapest, 1089, Hungary
  2. Department of Radiology, Semmelweis University, Budapest, Hungary
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Metabolic Diseases
  Orthopedics
  Internal Medicine
  
• 出版者：Springer Japan
• ISSN：1435-5604

文摘

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. Keywords Osteoporosis Wnt signaling Bone metabolism Genetic epidemiology