title: Association of the F352V variant of the Klotho gene with bone mineral density.
abstract: Klotho gene codes for a protein with glucuronidase activity and is thought to influence bone and vascular homeostasis. We studied the relationship of a common T/G polymorphism, resulting in a phenylalanine (F) to valine (V) substitution at aminoacid position 352, with bone mineral density (BMD) and osteoporotic fractures. The study group comprised 914 Spanish women, including 438 control subjects, 190 patients with osteoporosis, 198 with hip fractures, and 88 patients with severe osteoarthritis. BMD was measured by DEXA in 540 women from the control and osteoporosis groups. Allele frequencies were 86% and 14%, for the F and V alleles, respectively. In comparison with the most common FF genotype, postmenopausal women with FV/VV genotypes had higher hip BMD (femoral neck: 0.673 +/- 0.011 vs. 0.644 +/- 0.006 g/cm(2); P = 0.02; total hip: 0.807 +/- 0.014 vs. 0.774 +/- 0.008 g/cm(2); P = 0.03). Klotho alleles explained about 1.5% of BMD variance, but were not associated to the risk of osteoporotic spine or hip fractures. The Klotho genotype was not associated to BMD in premenopausal women. In conclusion, the F352V Klotho polymorphism is associated with BMD in postmenopausal women, suggesting that Klotho gene variants influence skeletal aging.
authors.affiliation: Department of Internal Medicine, Hospital U.M. Valdecilla, University of Cantabria, 39008 Santander, Spain. rianchoj@unican.es
authors.forename: José A
authors.initials: JA
authors.lastname: Riancho
authors.forename: Carmen
authors.initials: C
authors.lastname: Valero
authors.forename: José L
authors.initials: JL
authors.lastname: Hernández
authors.forename: Fernando
authors.initials: F
authors.lastname: Ortiz
authors.forename: Ana
authors.initials: A
authors.lastname: Zarrabeitia
authors.forename: María A
authors.initials: MA
authors.lastname: Alonso
authors.forename: Nicolás
authors.initials: N
authors.lastname: Peña
authors.forename: M Asunción
authors.initials: MA
authors.lastname: Pascual
authors.forename: Jesús
authors.initials: J
authors.lastname: González-Macías
authors.forename: María T
authors.initials: MT
authors.lastname: Zarrabeitia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D015519:Bone Density / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005966:Glucuronidase / Q000235:genetics*; D006620:Hip Fractures / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D000090265:Klotho Proteins; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics* / Q000503:physiopathology; D010024:Osteoporosis / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D010649:Phenylalanine; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D014633:Valine
chemical_list: D010649:Phenylalanine; D005966:Glucuronidase; D000090265:Klotho Proteins; D014633:Valine