title: Polymorphism of SLC25A32, the folate transporter gene, is associated with plasma folate levels and bone fractures in Japanese postmenopausal women.
abstract: OBJECTIVE
  Elevation of homocysteine is associated with an increased risk for bone fractures. We previously reported that the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism is associated with homocysteine levels and fracture. The association between the fracture and folate levels or their related gene polymorphisms is not completely clear. We speculated that the SLC25A32 gene, the mitochondrial inner membrane folate transporter, also could be implicated in the regulation of folate metabolism and fracture.
  
  
  METHODS
  A total of 851 Japanese postmenopausal women participated in the association study between the single nucleotide polymorphism genotype and plasma homocysteine or folate. We also tested the association between the candidate single nucleotide polymorphism and 663 postmenopausal women.
  
  
  RESULTS
  The AA genotype of rs2241777 single nucleotide polymorphism at the 3'UTR region in the SLC25A32 gene was associated with lower plasma folate concentration compared with the other genotypes in 851 postmenopausal women. A total of 674 postmenopausal ambulatory Japanese women were followed up for 5.5 ± 0.1 years (mean ± SE). The AA genotype groups also showed an apparently higher rate and earlier onset of incident fractures than the other genotypes. A total of 407 participants had >70% young-adult mean bone mineral density at the start of the observation.
  
  
  CONCLUSIONS
  These results show that the SLC25A32 gene polymorphism could be a risk factor for lower folate concentration and future fracture.
authors.affiliation: Department of Geriatric Medicine, The University of Tokyo, Tokyo, Japan; Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Urano
authors.forename: Masataka
authors.initials: M
authors.lastname: Shiraki
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Saito
authors.forename: Noriko
authors.initials: N
authors.lastname: Sasaki
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
mesh_terms: D015502:Absorptiometry, Photon; D015519:Bone Density; D004247:DNA / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D058972:Folic Acid Transporters; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017698:Postmenopause / Q000097:blood* / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D058972:Folic Acid Transporters; D026901:Membrane Transport Proteins; C417506:SLC25A32 protein, human; D004247:DNA; D005492:Folic Acid
keywords: SLC25A32; fracture; osteoporosis; single nucleotide polymorphism