Is Klotho F352V Polymorphism the Missing Piece of the Bone Loss Puzzle in Renal Transplant Recipients?

ÖZDEM S., YILMAZ V. T., ÖZDEM S. S., DÖNMEZ L., ÇETİNKAYA R., SÜLEYMANLAR G., ...Daha Fazla

PHARMACOLOGY, cilt.95, sa.5-6, ss.271-278, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 95 Sayı: 5-6
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1159/000398812
  • Dergi Adı: PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.271-278
  • Anahtar Kelimeler: Bone, Klotho polymorphism, Osteoporosis, Renal transplantation, AGED POSTMENOPAUSAL WOMEN, MINERAL DENSITY, KIDNEY-TRANSPLANTATION, VITAMIN-D, VERTEBRAL FRACTURES, FUNCTIONAL VARIANT, GENE POLYMORPHISMS, GRAFT RECIPIENTS, ASSOCIATION, OSTEOPOROSIS
  • Akdeniz Üniversitesi Adresli: Evet

Özet

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 1a-hydroxylase, and/or stimulate 24-hydroxylase in RT recipients. The resultant decrease 1,25D levels may participate in bone loss in these patients. (C) 2015 S. Karger AG, Basel