Analysis of lipid metabolism gene variants in individuals aged 25–44 years with contrasting LDL cholesterol levels

The increasing prevalence of low-density lipoprotein (LDL) hypercholesterolemia and its associated diseases among young people is a major public health concern in many countries. The aim of this study was to identify rare functionally significant variants in coding regions and adjacent splice sites of genes associated with elevated LDL cholesterol (LDL-C) levels in men and women aged 25–44 years. Methods . A population-based sample was stratified by deciles according to LDL-C concentration. The study included 146 individuals with LDL-C <2.1 mmol/L (first decile) and 158 individuals with LDL-C ≥ 4.2 mmol/L (tenth decile). Targeted high-throughput sequencing was performed. Results . In the sample of young adults, 0.07 % had LDL-C levels >8.5 mmol/L, 0.13 % had levels ranging from 6.5 to 8.4 mmol/L, and 2.25 % had levels between 5.0 and 6.4 mmol/L. Participants in the first and tenth LDL-C deciles differed in the spectrum of variants in lipid metabolism genes. Functionally significant variants associated with LDL hypercholesterolemia were identified in individuals with LDL-C ≥4.2 mmol/L in the coding regions of the LDLR and APOB genes, as well as in ABCA1, LCAT, LIPA, LIPC, and LPA. Conclusions . Rare functionally significant variants in coding regions and adjacent splice sites of genes associated with elevated LDL-C levels were identified in young men and women.