Mosaic Loss of Y Chromosome: Temporal Variance and Association with Various Features in Patients at High Risk of Cardiovascular Disease

Mosaic loss of the Y chromosome (mLOY) is a common karyotype alteration. The accumulation of LOY cells leads to genetic mosaicism and affects the development of pathological conditions in elderly men. Emerging data suggest that this phenomenon might be associated with an increased risk of cardiovascular disease (CVD) and several clinical and demographic parameters. However, the short-term dynamics of mLOY remain insufficiently investigated. Therefore, this study aimed to evaluate the short-term dynamics of mLOY in peripheral blood and its association with various features in men with high CVD risk. The study included healthy young volunteers (control group; n = 48) and male patients with a high risk of cardiovascular disease (HCR group; n = 65). Peripheral blood was obtained for the mLOY analysis from the HCR group at two time points: initially and after 6 months. mLOY was analyzed using a self-designed assay targeting SRY and EIF2C1 as a reference for digital droplet PCR. This assay demonstrated a high degree of linearity for Y chromosome copy numbers (CNs) from 0.9 to 0.6 (R2 = 0.9986) in mLOY models. In the control group, the CNs varied from 0.9 to 1.1. mLOY was detected in 6 of 65 patients in the HCR group (CNs below 0.9). This study revealed preliminary, hypothesis-generating associations between mLOY and sedentary lifestyle and family history of early-onset CVDs (p < 0.05; however, the former did not retain significance after adjusting for age). Analysis of temporal variations of mLOY demonstrated heterogeneous dynamics: in some patients, mLOY resolved, whereas in others, Y chromosome CN decreased even further with time. However, given the low mLOY incidence rate in the investigated cohort, these results should be considered preliminary and exploratory. Further studies are warranted to determine the potential utility of mLOY and its temporal dynamics for assessing CVD risk.