Klotho polymorphisms, FGF23 and mortality among elderly men (Swedish MrOs).
(English)Manuscript (preprint) (Other academic)
Westerberg, P-A and Kindmark, A contributed equally in preparation of the manuscript.
Introduction. α-Klotho is the co receptor for Fibroblast growth factor(FGF)23and crucial for phosphate and vitamin D metabolism. Variants in the KLOTHO (KL) gene are associated with longevity and cardiovascular morbidities. Primary aim of this study is to examine if variations in KL affect mortality risk in a cohort of elderly men. Secondary aims are to examine associations with serum levels of FGF23, phosphate and renal function.
Methods and results. 27 single nucleotide polymorphisms (SNP) in KLOTHO were genotyped using single base primer extension mass array technique on samples from 2924 men, aged 69 to 81 years, included in Swedish MrOs. After in average 6.1 years of follow up 584 had died, 214 of cardiovascular cause. After quality analyses and tagging of haplotypes 11 SNPs were analyzed for variation in mortality risk, serum levels of FGF23, phosphate, calcium and renal function. There were no associations with mortality of all cause. One SNP, (rs398655), in proximity to the promoter, demonstrated an increased Hazard ratio (95% Confidence interval(CI)) of 53% (95% CI, 8-118%) for death due to CVD in heterozygotes compared to homozygotes. Analysis using a dominant model showed an association between SNPs in the 5’ end of the gene and eGFR, phosphate level and logFGF23 (P=0.01).
Conclusion. KL polymorphisms are associated with variation in FGF23 and phosphate.
Klotho, FGF23, mineral metabolism, phosphatonin, mortality, elderly
Other Basic Medicine
IdentifiersURN: urn:nbn:se:uu:diva-188225OAI: oai:DiVA.org:uu-188225DiVA: diva2:576846