Familial hypobetalipoproteinemia: spectrum of variants and phenotypic manifestations

Abstract

Variants in the APOB gene are associated with the development of familial hypobetalipoproteinemia (FHBL), variants in the PCSK9, ANGPTL3, ANGPTL4, MTTP and SAR1B genes cause phenotypes similar to FHBL. The aim was to investigate the spectrum of variants associated with FHBL and other similar phenotypes in the «NMRC TPM» sample. The study sample: ESSE-RF participants (n = 3070) and patients of the Expert Center for Hereditary Dyslipidemias (n = 3063). Based on NGS data, the above genes associated with lipid metabolism disorders were analyzed, and the genetic risk scale (GRS) values of low-density lipoprotein cholesterol (LDL-C) were evaluated. A total of 20 variants were found in 34 individuals associated with the phenotypes under study, including 10 variants in the APOB gene (10 individuals), 3 in the PCSK9 gene (4 individuals), 3 in the ANGPTL3 gene (3 individuals), and 4 in the ANGPTL4 gene (17 individuals). All variants were detected in the heterozygous state. In 5 individuals, the LDL-C GHR value was below the 10th percentile. The median LDL-C value in the group was 2,31 (1,52 – 3,03) mmol/L. Carriers of variants in the APOB gene had significantly lower LDL-C levels than carriers of variants in other genes: 1.19±0.72 mmol/L and 2.69±1.09 mmol/L, respectively, p<0.001.