title: Is Klotho F352V Polymorphism the Missing Piece of the Bone Loss Puzzle in Renal Transplant Recipients?
abstract: BACKGROUND
  Bone disorders are next to cardiovascular problems in frequency in renal transplant (RT) recipients. Reduction in 1,25-dihydroxycholecalciferol (1,25D) levels is among the reasons causing bone loss in these patients. Klotho (KL) serves as a co-receptor for fibroblast growth factor 23 (FGF23), and functions in vitamin D metabolism. KL polymorphisms have been identified in several studies, and phenylalanine to valine substitution at amino acid position 352 seemed to be important to KL function. We investigated KL F352V polymorphism and its relation with 1,25D levels in RT recipients.
  
  
  METHODS
  The study included 25 RT recipients (8 female, 17 male) and 26 (14 female, 12 male) healthy control subjects who were wild (FF) phenotypes in terms of KL F352V polymorphism. RT recipients with (FV, n = 11) and without (FF, n = 14) a heterozygote polymorphism were determined with high resolution DNA melting analysis of KL F352V polymorphism. Serum 1,25D levels were measured using the RIA method.
  
  
  RESULTS
  RT recipients with FV phenotype had significantly lower 1,25D levels (17.58 ± 18.38 pg/ml) compared to recipients with FF phenotype (44.91 ± 24.68 pg/ml) and control subjects (28.24 ± 12.13 pg/ml). 1,25D levels in RT recipients with FF phenotype were significantly higher than control subjects.
  
  
  CONCLUSIONS
  KL F352V polymorphism may increase the expression of FGF23 co-receptor, KL protein and thus may decrease renal expression of 1α-hydroxylase, and/or stimulate 24-hydroxylase in RT recipients. The resultant decrease 1,25D levels may participate in bone loss in these patients.
authors.affiliation: Departments of Medical Biochemistry, Akdeniz University Medical School, Antalya, Turkey.
authors.forename: Sebahat
authors.initials: S
authors.lastname: Ozdem
authors.forename: Vural Taner
authors.initials: VT
authors.lastname: Yılmaz
authors.forename: Sadi S
authors.initials: SS
authors.lastname: Ozdem
authors.forename: Levent
authors.initials: L
authors.lastname: Donmez
authors.forename: Ramazan
authors.initials: R
authors.lastname: Cetinkaya
authors.forename: Gultekin
authors.initials: G
authors.lastname: Suleymanlar
authors.forename: F Fevzi
authors.initials: FF
authors.lastname: Ersoy
mesh_terms: D000328:Adult; D001862:Bone Resorption / Q000097:blood / Q000235:genetics*; D002117:Calcitriol / Q000097:blood; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005966:Glucuronidase / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D002117:Calcitriol