Přehled o publikaci

Elevated low-density lipoprotein cholesterol (LDL-C) levels in childhood is a major risk factor for premature cardiovascular disease (CVD). While monogenic familial hypercholesterolemia is well recognized, a significant proportion of patients with elevated LDL-C levels have polygenic cause of their condition. Polygenic risk score (PRS) that aggregates the impact of multiple common variants associated with LDL-C levels is commonly used to characterise polygenic hypercholesterolemia. Lipoprotein(a) (Lp(a)), an LDL-like particle containing apolipoprotein(a), represents additional CVD risk. Lp(a) levels are predominantly determined by genetic factors. Elevated Lp(a) can contribute to measured LDL-C and potentially confound its interpretation. In this study, we analysed umbilical cord blood samples from pilot newborn screening project. For nearly 6000 newborns, the LDL-C levels were measured at study enrolment and LDL-C level percentiles were ascertained. For individuals with low (0-15th percentile), medium (40-60th percentile) and high (75-100th percentile) LDL-C levels, we analysed the PRS and Lp(a) values. PRS and Lp(a) were assessed as independent genetic risk factors for elevated LDL-C. Preliminary results show statistically significant differences in PRS and Lp(a) levels between groups with low, medium, and high LDL-C. Results indicate that evaluation of PRS and Lp(a) measurement are important, as both may contribute to explaining elevated LDL-C levels in individuals with hypercholesterolemia.