title: CYP2C9 genotype and association with bone mineral density: a pilot study.
abstract: BACKGROUND
  In recent years reduced bone mineral density (BMD) and osteoporosis have become major public health problems. Single nucleotide polymorphisms (SNPs) in the cytochrome P450 2C9 (CYP2C9) gene influence the response to oral anticoagulant drugs, which are positively associated with the risk to develop osteoporosis. The aim of the present investigation was to clarify a potential role of CYP2C9 sequence variations and susceptibility to develop osteoporosis.
  
  
  METHODS
  Ninety two consecutive angiologic outpatients, mean age: 60.3±14.4, without secondary causes of bone loss were genotyped and classified as patients with normal BMD, osteopenia and osteoporosis according to WHO criteria by dual-energy X-ray absorptiometry at the lumbar spine and/or the femoral neck. Potential association between the CYP2C9 genotype and BMD was tested.
  
  
  RESULTS
  59% of the patients (n=54) presented with reduced BMD and were compared to 38 age-matched persons with normal BMD. The genotype distribution showed 15% heterozygous for CYP2C9*2 p.Arg144Cys, 14% for CYP2C9*3 p.IIe359Leu, 2% for both polymorphisms, and 69% had wildtype genotypes. Patients with CYP2C9 mutations had significantly lower BMD values at the femoral neck and displayed a four-fold higher adjusted risk to suffer from reduced BMD than individuals with wildtype genotypes (p=0.02).
  
  
  CONCLUSIONS
  Oral anticoagulant treatment is common in angiologic outpatients. The gene variants CYP2C9*2 and CYP2C9*3 have been shown to require lower maintenance doses of oral anticoagulant drugs. An association between oral anticoagulant drugs and the susceptibility to develop osteoporosis in relation to sequence variations in the CYP2C9 gene is suggested to be mediated via the glucocorticoid synthesis pathway.
  
  
  CONCLUSIONS
  The CYP2C9*2/CYP2C9*3 variants were significantly associated with femoral BMD in a selected elderly Austrian population. These variants could contribute to the complex risk to develop osteoporosis.
authors.affiliation: Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria. sophie.ziegler@meduniwien.ac.at
authors.forename: Sophie
authors.initials: S
authors.lastname: Brunner-Ziegler
authors.forename: Georgiana-Aura
authors.initials: GA
authors.lastname: Giurgea
authors.forename: Raute
authors.initials: R
authors.lastname: Sunder-Plassmann
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hammer
authors.forename: Christian
authors.initials: C
authors.lastname: Margeta
authors.forename: Martin
authors.initials: M
authors.lastname: Brunner
authors.forename: Renate
authors.initials: R
authors.lastname: Koppensteiner
authors.forename: Christine
authors.initials: C
authors.lastname: Mannhalter
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001315:Australia; D015992:Body Mass Index; D015519:Bone Density / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010865:Pilot Projects; D012737:Sex Factors
chemical_list: C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases
keywords: BMD; BMI; CYP2C9; CYP2C9 mutation; DEXA; Glucocorticoid synthesis; Oral anticoagulant treatment; Osteoporosis; SNP; body mass index; bone mineral density; cytochrome P450 2C9; dual-energy X-ray absorptiometry; single nucleotide polymorphism