Epigenetic aging signatures in people with hemophilia

Introduction: Hemophilia is a rare X-linked bleeding disorder leading to recurrent hemarthroses, hemophilic arthropathy, and impaired quality of life. A chronic lifelong disease, hemophilia might be associated with accelerated biological aging. Epigenetic age estimators using cytosine methylation in cytosine-phosphate-guanine (CpG) dinucleotides have been suggested to reflect biological age. Patient/Methods: We collected blood samples from men with severe (PWSH, n=20) or mild hemophilia (PWMH, n=20), and age-matched healthy male controls (n=20). DNA methylation of CpGs at five genes (ASPA, ITGA2B, PDE4C, FHL2, CCDC10SB) were measured by bisulfite pyrosequencing. Biological age was estimated using two epigenetic aging signatures, each including three CpGs (3-CpG age estimators). We investigated differences in biological age and the rate of biological aging between study groups using separate linear regressions on chronological age and study group without and with an interaction, respectively. Results: Deviations of epigenetic from chronological age were high for both 3-CpG age estimators, with results suggesting systematic over-prediction. In both linear regressions using the two 3-CpG estimates, respectively, evidence for a different rate of biological aging in severe hemophilia was weak. The rate of biological aging in PWSH was 0.24 (95%CI, 0.01 to 0.48) and 0.21 (0.04 to 0.37) higher compared to PWMH, and 0.05 (-0.19 to 0.29) and 0.17 (-0.00 to 0.34) higher compared to healthy controls, respectively. Hemophilic arthropathy was associated with an increased rate of biological aging. Conclusion: Evidence for a difference in epigenetic aging as reflected by two 3-CpG estimators in severe compared to mild hemophilia or healthy controls was weak.