Association of dyslipidemia with single nucleotide polymorphisms of the cholesteryl ester transfer protein gene and cardiovascular disease risk factors in a highly admixed population

Author(s)

Leite, Jean Michel R. S. ; Pereira, Jaqueline L. ; Damasceno, Nagila R. T. ; Soler, Julia M. Pavan ; Fisberg, Regina M. ; Rogero, Marcelo M. ; Sarti, Flavia M.

• Document type: Journal article
• Source: CLINICAL NUTRITION ESPEN; v. 58, p. 11-pg., 2023-10-19.

Abstract

Background and aims: Cardiovascular diseases (CVD) are major causes of mortality worldwide, leading to premature deaths, loss of quality of life, and extensive socioeconomic impacts. Alterations in normal plasma lipid concentrations comprise important risk factors associated with CVD due to mechanisms involved in the pathophysiology of atherosclerosis. Genetic markers such as single nucleotide poly-morphisms (SNPs) are known to be associated with lipid metabolism, including variants in the choles-teryl ester transfer protein (CETP) gene. Thus, the study's objective was to assess the relationship among lipid profile, socioeconomic and demographic characteristics, health status, inflammatory biomarkers, and CETP genetic variants in individuals living in a highly admixed population.Methods: The study comprises an analysis of observational cross-sectional data representative at the population level from a highly admixed population, encompassing 901 individuals from three age groups (adolescents, adults, and older adults). Socioeconomic, demographic, health, and lifestyle characteristics were collected using semi-structured questionnaires. In addition, biochemical markers and lipid profiles were obtained from individuals' blood samples. After DNA extraction, genotyping, and quality control according to Affymetrix's guidelines, information on 15 SNPs in the CETP gene was available for 707 individuals. Lipid profile and CVD risk factors were evaluated by principal component analysis (PCA), and associations between lipid traits and those factors were assessed through multiple linear regression and logistic regression.Results: There were low linear correlations between lipid profile and other individuals' characteristics. Two principal components were responsible for 80.8 % of the total variance, and there were minor differences in lipid profiles among individuals in different age groups. Non-HDL-c, total cholesterol, and LDL-c had the highest loadings in the first PC, and triacylglycerols, VLDL-c and HDL-c were responsible for a major part of the loading in the second PC;, whilst HDL-c and LDL-c/HDL-c ratio were significant in the third PC. In addition, there were minor differences between groups of individuals with or without dyslipidemia regarding inflammatory biomarkers (IL-1b, IL-6, IL-10, TNF-a, CRP, and MCP-1). Being overweight, insulin resistance, and lifestyle characteristics (calories from solid fat, added sugar, alcohol and sodium, leisure physical activity, and smoking) were strong predictors of lipid traits, especially HDL-c and dyslipidemia (p < 0.05). The CETP SNPs rs7499892 and rs12691052, rs291044, and rs80180245 were significantly associated with HDL-c (p < 0.05), and their inclusion in the multiple linear regression model increased its accuracy (adjusted R-2 rose from 0.12 to 0.18).Conclusion: This study identified correlations between lipid traits and other CVD risk factors. In addition, similar lipid and inflammatory profiles across age groups in the population suggested that adolescents might already present a significant risk for developing cardiovascular diseases in the population. The risk can be primarily attributed to decreased HDL-c concentrations, which appear to be influenced by genetic factors, as evidenced by associations between SNPs in the CETP gene and HDL-c concentrations, as well as potential gene-diet interactions. Our findings underscore the significant impact of genetic and lifestyle factors on lipid profile within admixed populations in developing countries. (c) 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 20/15899-2 - Association between dyslipidemias and health costs at population level: Polygenic risk scores and modeling through computational microsimulation.
• Grantee: Jean Michel Rocha Sampaio Leite
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/22113-9 - Biochemical indicators of micronutrient status and usual intakes of residents from the City of São Paulo - ISA-Capital Survey 2013
• Grantee: Regina Mara Fisberg
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/05125-7 - Lifestyle, biochemical and genetic markers as cardiometabolic risk factors: Health Survey in São Paulo City
• Grantee: Regina Mara Fisberg
• Support Opportunities: Research Projects - Thematic Grants