Frequencies of variants in genes associated with dyslipidemias identified in Costa Rican genomes.

Abstract

Dyslipidemias are risk factors in diseases of significant importance to public health, such as atherosclerosis, a condition that contributes to the development of cardiovascular disease. Unhealthy lifestyles, the pre-existence of diseases, and the accumulation of genetic variants in some loci contribute to the development of dyslipidemia. The genetic causality behind these diseases has been studied primarily on populations with extensive European ancestry. Only some studies have explored this topic in Costa Rica, and none have focused on identifying variants that can alter blood lipid levels and quantifying their frequency. To fill this gap, this study focused on identifying variants in 69 genes involved in lipid metabolism using genomes from two studies in Costa Rica. We contrasted the allelic frequencies with those of groups reported in the 1000 Genomes Project and gnomAD and identified potential variants that could influence the development of dyslipidemias. In total, we detected 2,600 variants in the evaluated regions. However, after various filtering steps, we obtained 18 variants that have the potential to alter the function of 16 genes, nine variants have pharmacogenomic or protective implications, eight have high risk in Variant Effect Predictor, and eight were found in other Latin American genetic studies of lipid alterations and the development of dyslipidemia. Some of these variants have been linked to changes in blood lipid levels in other global studies and databases. In future studies, we propose to confirm at least 40 variants of interest from 23 genes in a larger cohort from Costa Rica and Latin American populations to determine their relevance regarding the genetic burden for dyslipidemia. Additionally, more complex studies should arise that include diverse clinical, environmental, and genetic data from patients and controls and functional validation of the variants.