Valverde-Hernández Juan Carlos, Flores-Cruz Andrés, Chavarría-Soley Gabriela, Silva de la Fuente Sandra, Campos-Sánchez Rebeca
Centro de Investigación en Biología Celular y Molecular, University of Costa Rica, San José, Costa Rica.
Escuela de Biología, University of Costa Rica, San José, Costa Rica.
Front Genet. 2023 Mar 30;14:1114774. doi: 10.3389/fgene.2023.1114774. eCollection 2023.
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 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.
血脂异常是对公众健康至关重要的疾病的危险因素，如动脉粥样硬化，这种病症会促进心血管疾病的发展。不健康的生活方式、疾病的预先存在以及某些基因变异的积累都有助于血脂异常的发展。这些疾病背后的遗传因果关系主要在欧洲血统广泛的人群中进行了研究。在哥斯达黎加，只有一些研究探讨了这个话题，而且没有一项研究专注于识别能够改变血脂水平并量化其频率的变异。为了填补这一空白，本研究利用哥斯达黎加两项研究中的基因组，专注于识别参与脂质代谢的69个基因中的变异。我们将等位基因频率与千人基因组计划和gnomAD中报告的群体的等位基因频率进行了对比，并确定了可能影响血脂异常发展的潜在变异。总共，我们在评估区域检测到2600个变异。然而，经过各种筛选步骤后，我们获得了18个有可能改变16个基因功能的变异，9个变异具有药物基因组学或保护意义，8个在变异效应预测器中有高风险，8个在其他关于脂质改变和血脂异常发展的拉丁美洲遗传研究中被发现。在其他全球研究和数据库中，其中一些变异已与血脂水平的变化有关。在未来的研究中，我们建议在来自哥斯达黎加和拉丁美洲人群的更大队列中确认至少40个来自23个基因的感兴趣变异，以确定它们与血脂异常遗传负担的相关性。此外，应该开展更复杂的研究，包括来自患者和对照的多样化临床、环境和遗传数据以及变异的功能验证。
