title: Bone mineral density is associated with vitamin D related rs6013897 and estrogen receptor polymorphism rs4870044: The Tromsø study.
abstract: BACKGROUND
  Bone mineral density (BMD) is determined by bone remodeling processes regulated by endocrine, autocrine and genetic mechanisms. Thus, some studies have reported that BMD is associated with single nucleotide polymorphisms (SNPs) associated with vitamin D receptor (VDR), serum 25(OH)D levels and estrogen receptor 1 (ESR1), but without consensus. Therefore, we aimed to map and compare the risk genotypes for forearm and total hip low BMD.
  
  
  RESULTS
  Data were derived from a population-based study in northern Norway; the Tromsø Study. Distal forearm BMD was measured with a single x-ray absorptiometric device, while total hip BMD was measured with a dual-energy x-ray absorptiometric device. There were 7,317 and 4,082 successful analyses of distal forearm and total hip BMD, respectively, and at least one SNP of interest. We evaluated plausible BMD modulating factors and associations of BMD and SNPs related to vitamin D metabolism (FokI, Cdx2, BsmI, rs2298850, rs10741657, rs3794060, rs6013897), ApaI-BsmI-TaqI haplotypes and ESR1 SNP rs4870044.
  
  
  RESULTS
  Age, BMI, physical activity and smoking were significantly associated with BMD. In a linear regression model with adjustment for age and gender and with the major homozygote as reference, rs6013897 had a standardized beta coefficient (β) of -0.031 (P = 0.024) for total hip BMD. β for ESR1 SNP rs4870044 was -0.016 (P = 0.036) for forearm BMD and -0.034 (P = 0.015) for total hip BMD. The other SNPs nor serum 25(OH)D were significantly associated with BMD.
  
  
  CONCLUSIONS
  Both forearm and total hip BMD were associated with ESR1 SNP rs4870044. Of the vitamin D-related genes, only CYP24A1 gene rs6013897 was associated with total hip BMD, but the association was weak and needs confirmation in other studies. Serum 25(OH)D was not associated with BMD in our population, probably due to the generally sufficient vitamin D levels in the population.
authors.affiliation: Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Ieva
authors.identifier: http://orcid.org/0000-0002-6873-2852
authors.initials: I
authors.lastname: Martinaityte
authors.affiliation: Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Rolf
authors.initials: R
authors.lastname: Jorde
authors.affiliation: Department of Health and Care Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Nina
authors.initials: N
authors.lastname: Emaus
authors.affiliation: Epidemiology of chronic diseases research group, Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Anne Elise
authors.initials: AE
authors.lastname: Eggen
authors.affiliation: Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Ragnar Martin
authors.initials: RM
authors.lastname: Joakimsen
authors.affiliation: Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Elena
authors.initials: E
authors.lastname: Kamycheva
mesh_terms: D000328:Adult; D015519:Bone Density; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009664:Norway; D020641:Polymorphism, Single Nucleotide; D014807:Vitamin D / Q000097:blood*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D014807:Vitamin D