Original Research

Calcified Tissue International

, Volume 91, Issue 1, pp 15-23

Novel Sequence Variations in the CER1 Gene Are Strongly Associated with Low Bone Mineral Density and Risk of Osteoporotic Fracture in Postmenopausal Women

  • Theodora KoromilaAffiliated withLaboratory of Human Genetics, Department of Biology, University of Athens Email author 
  • , Zoe DailianaAffiliated withDepartment of Orthopedic Surgery, Faculty of Medicine, University of Thessalia
  • , Stavroula SamaraAffiliated withLaboratory of Medical Genetics and Cytogenetics, Faculty of Medicine, University of Thessalia
  • , Chris ChassanidisAffiliated withLaboratory of Medical Genetics and Cytogenetics, Faculty of Medicine, University of Thessalia
  • , Chara TzavaraAffiliated withLaboratory of Human Genetics, Department of Biology, University of Athens
  • , George P. PatrinosAffiliated withDepartment of Pharmacy, Faculty of Health Sciences, University Campus, University of Patras
  • , Vassiliki Aleporou-MarinouAffiliated withLaboratory of Human Genetics, Department of Biology, University of Athens
  • , Panagoula KolliaAffiliated withLaboratory of Human Genetics, Department of Biology, University of Athens

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Abstract

Osteoporosis is a common skeletal disease characterized by a combination of low bone mass and increased fragility. In this case–control study, we investigated the possible association of two novel candidate genes, CER1 and TOB1, with bone mineral density (BMD) and fragility risk in 300 postmenopausal women of Hellenic origin. The entire CER1 and TOB1 gene sequences were amplified and resequenced to assess whether there is a correlation between these genes and BMD. We identified 26 variants in both genes. Statistical analysis did not reveal any correlation between TOB1 and osteoporosis. However, CER1 genetic analysis indicated that five polymorphisms, c.194C>G, c.507+506G>T, c.508−182A>G, c.531A>G, and c.*121T>C, were correlated, with a mean T score ≤–2.2. In particular, the greater number of vertebral fractures was found in patients with osteoporosis carrying the G allele of c.531A>G SNP (p = 0.015). When multiple logistic regression analysis was performed, only the c.507+506G>T polymorphism was independently associated with hip fractures or the presence of any fracture (OR = 6.95, p = 0.016, and OR = 5.33, p < 0.001, respectively). These results suggest that CER1 gene variations play a significant role in determining BMD and vertebral or hip fractures, which might be helpful in clinical practice to identify patients with increased fracture risk.

Keywords

Dual-energy X-ray absorptiometry Bone morphogenetic protein Transforming growth factor Osteoporosis Genetic polymorphism Fracture