Hipercolesterolemia Familiar: caracterização molecular e sua relação com novos marcadores de risco cardiovascular

Abstract

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by elevated levels of low-density lipoprotein cholesterol (LDLc). Lately, lipoprotein (a) [Lp(a)] has gained importance in the study of individuals carrying genetic variants related to FH. The detection of genetic variants in index cases (IC), and the cascade evaluation of 1st and 2nd degree relatives, can provide an early diagnosis to reduce unfavorable outcomes in this population. The aim of this study was to genetically characterize IC with clinical criteria for FH and their relatives, as well as to evaluate new cardiovascular risk markers (GDF-15, CXCL16, FABP3, FABP4, LIGHT, sCD14, ucMGP and microparticles-MPs) in these individuals according to the presence of genetic variants. A total of 137 individuals were evaluated, 17 of which were IC with identified variants for FH and 120 family members, living in the region of Bom Despacho – MG. Genetic sequencing was performed by Next Generation Sequencing (NGS) for IC and by the Sanger method for relatives. LDLc was determined by colorimetric method, Lp(a) by turbidimetry, new markers of cardiovascular risk by multiplex method for Luminex and microparticles by flow cytometry. Statistical analyzes were performed using the R Platform version 4.2.2 program. Seven genetic variants were identified, with 86 carrier individuals, the majority in the LDLR gene, and 51 family members who did not carry the researched variants. Lp(a) showed a significant difference between groups, with higher levels found in the group with variants. GDF-15, CXCL16, LIGHT, sCD14 and ucMGP markers did not show significant difference between groups, even when analyzed by the influence of statin treatment. However, FABP3 and FABP4 showed a significant difference, with higher levels in the group without genetic variants and using statins. Higher counts of total MPs, microparticles derived from cardiomyocytes, endothelium and those expressing tissue factor were observed in the group carrying genetic variants. In addition, the FH group not using statins had higher counts of these MPs when compared to the group without FH. In conclusion, genetic variants are associated with FH in the studied population, and the new cardiovascular risk markers – FABP3, FABP4 and MPs – showed potential in identifying carriers of genetic variants related to FH, which may be useful in the early identification of the disease in a population at risk, in the absence of genetic testing.