title: The genetic background of osteoporosis in cystic fibrosis: association analysis with polymorphic markers in four candidate genes.
abstract: BACKGROUND
  Reduced Bone Mass Density (BMD) is frequent in Cystic Fibrosis (CF). Potentially, other genes than the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene may contribute to the bone phenotype variability in CF patients.
  
  
  METHODS
  Four candidate genes likely associated with BMD variability were studied: the vitamin D receptor (VDR) gene, the estrogen receptor alpha (ESR1), the calcitonin receptor (CALCR) and the type I alpha 1 collagen (COL1A1) gene. A complete bone and CF evaluation was obtained for 82 subjects (39 m, 43 f): 15 had normal BMD (group 1), 46 were osteopenic (group 2), and 21 were osteoporotic (group 3).
  
  
  RESULTS
  No statistical difference was found among the three groups for age, sex, pancreatic status, and vertebral fractures, nor for any of the biochemical markers. Weight, Body Mass Index (BMI), and FEV1, scored significantly worse in the two groups with the lowest T score. The CFTR mutations R1162X and F508del were more frequent in patients with lower BMD (p=0.044 and p=0.071). There was no significant difference in the distribution of the five marker genotypes among the 3 groups defined according to the unadjusted or adjusted (BMI and FEV1) BMD T score. No significant correlation was found between the VDR, CALCR, or COL1A1 gene polymorphisms and reduced BMD values. The individual ESR1 PvuII-XbaI haplotype C-A is associated to elevated u-calcium levels whereas the haplotype T-A is associated to lower values (p=0.00251).
  
  
  CONCLUSIONS
  There was no evidence that the genes under study, with the possible exception of ESR1 gene variants, may modulate bone phenotype in CF.
authors.affiliation: Cystic Fibrosis Center, Pediatric Department, Azienda Ospedaliera, Verona, Italy. carlo.castellani@azosp.vr.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Castellani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Malerba
authors.forename: Antonella
authors.initials: A
authors.lastname: Sangalli
authors.forename: Antonella
authors.initials: A
authors.lastname: Delmarco
authors.forename: Elena
authors.initials: E
authors.lastname: Petrelli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Rossini
authors.forename: Baroukh M
authors.initials: BM
authors.lastname: Assael
authors.forename: Monica
authors.initials: M
authors.lastname: Mottes
mesh_terms: D000328:Adult; D024042:Collagen Type I / Q000235:genetics; D003550:Cystic Fibrosis / Q000150:complications* / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D003720:Densitometry; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000150:complications* / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011859:Radiography; D018003:Receptors, Calcitonin / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics; D013131:Spine / Q000000981:diagnostic imaging
chemical_list: C505032:CFTR protein, human; D024042:Collagen Type I; D047628:Estrogen Receptor alpha; D005819:Genetic Markers; D018003:Receptors, Calcitonin; D018167:Receptors, Calcitriol; D019005:Cystic Fibrosis Transmembrane Conductance Regulator