Klotho variants and chronic hemodialysis mortality.
Journal Article (Journal Article)
Patients with end-stage renal disease (ESRD) suffer exceptionally high mortality rates in their first year of chronic hemodialysis. Both vitamin D and fibroblast growth factor (FGF)-23 levels correlate with survival in these patients. Klotho is a protein in the vitamin D/FGF-23 signaling pathway that has been linked with accelerated aging and early mortality in animal models. We therefore hypothesized that genetic variation in the Klotho gene might be associated with survival in subjects with ESRD. We tested the association between 12 single nucleotide polymorphisms (SNPs) in the Klotho gene and mortality in a cohort of ESRD patients during their first year on hemodialysis (n = 1307 white and Asian). We found a significant association between the CC genotype of one tag SNP, rs577912, and increased risk for 1-yr mortality (RR, 1.76; 95% CI, 1.19-2.59; p = 0.003). This effect was even more marked among patients who were not treated with activated vitamin D supplementation (HR, 2.51; 95% CI, 1.18-5.34; p = 0.005). In lymphoblastoid cell lines derived from HapMap subjects, the CC genotype was associated with a 16-21% lower Klotho expression compared with the AA/AC genotype. Our data suggest that a specific Klotho variant (rs577912) is linked to survival in ESRD patients initiating chronic hemodialysis and that therapy with activated vitamin D may modify this risk.
Full Text
Duke Authors
Cited Authors
- Friedman, DJ; Afkarian, M; Tamez, H; Bhan, I; Isakova, T; Wolf, M; Ankers, E; Ye, J; Tonelli, M; Zoccali, C; Kuro-o, M; Moe, O; Karumanchi, SA; Thadhani, R
Published Date
- November 2009
Published In
Volume / Issue
- 24 / 11
Start / End Page
- 1847 - 1855
PubMed ID
- 19419323
Pubmed Central ID
- PMC2765930
Electronic International Standard Serial Number (EISSN)
- 1523-4681
Digital Object Identifier (DOI)
- 10.1359/jbmr.090516
Language
- eng
Conference Location
- United States