Abstract
Introduction
The core features of obstructive sleep apnea (OSA) can potentially contribute to the acceleration of telomere shortening mechanisms. Among these factors, klotho reduction can contribute since it is associated with accelerated systemic inflammation and oxidative stress and has recently been associated with OSA. Also, decreased levels of klotho are implicated in the regulation of telomerase activity. Therefore, we aimed to evaluate the effect of common genetic variants (SNPs) on KLOTHO gene on the association between OSA and short telomere length.
Methods
As part of the Sao Paulo Epidemiologic Sleep Study cohort, 1,042 individuals answered questionnaires, underwent polysomnography and had blood collected for DNA extraction. OSA was defined according to AHI equal or greater than 15 events per hour. Leukocyte telomere length (LTL) was measured through qPCR and SNPs were genotyped by microarray.
Results
LTL was significantly shorter in OSA compared to controls in a severity-dependent manner (B=0.055, CI=0.007–0.102, p=0.02). Among the 43 SNPs analyzed, we observed that 4 SNPs (rs525014, rs7982726, rs685417 and rs9563124) significantly mediated the association between OSA and short LTL (B=0.046, df=1, p=0.005; B=0.044, df=1, p=0.007; B=0.045, df=1, p=0.006; B=0.044, df=1, p=0.007; respectively). Furthermore, this association was under an additive model since having one or two alleles of the alternative variants were significantly associated with shorter LTL.
Conclusion
We could conclude that klotho opens a new venue in OSA research and would be applicable to prevent the consequences of short telomeres in individuals with OSA.
Support
This work was supported by grants from AFIP, FAPESP and CAPES.
0022 Klotho Genetic Variants Mediate the Association Between Obstructive Sleep Apnea and Short Telomere Length
