Abstract
Background and Aim Individual lipid phenotypes including circulating total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triglycerides (TG) determinations are influenced by gene-environment interactions. The aim of this study was to predict blood lipid level (TC, LDL-c, HDL-c, and TG) variability using genetic and lifestyle data in subjects with excessive body weight-for-height. Methods This cross-sectional study enrolled 304 unrelated overweight/obese adults of self-reported European ancestry. A total of 95 single nucleotide polymorphisms (SNPs) related to obesity and weight loss were analyzed by a targeted next-generation sequencing system. Relevant genotypes of each SNP were coded as 0 (nonrisk) and 1 (risk). Four genetic risk scores (GRS) for each lipid phenotype were calculated by adding the risk genotypes. Information concerning lifestyle (diet, physical activity, alcohol drinking, and smoking) was obtained using validated questionnaires. Total body fat (TFAT) and visceral fat (VFAT) were determined by dual-energy X-ray absorptiometry. Results Overall, 45 obesity-related genetic variants were associated with some of the studied blood lipids. In addition to conventional factors (age, sex, dietary intakes, and alcohol consumption), the calculated GRS significantly contributed to explain their corresponding plasma lipid trait. Thus, HDL-c, TG, TC, and LDL-c serum concentrations were predicted by approximately 28% (optimism-corrected adj. R 2 = 0.28), 25% (optimism-corrected adj. R 2 = 0.25), 24% (optimism-corrected adj. R 2 = 0.24), and 21% (optimism-corrected adj. R 2=0.21), respectively. Interestingly, GRS were the greatest contributors to TC (squared partial correlation (PC2) = 0.18) and LDL-c (PC2 = 0.18) features. Likewise, VFAT and GRS had a higher impact on HDL-c (PC2 = 0.09 and PC2 = 0.06, respectively) and TG levels (PC2 = 0.20 and PC2 = 0.07, respectively) than the rest of variables. Conclusions Besides known lifestyle influences, some obesity-related genetic variants could help to predict blood lipid phenotypes.
Highlights
Triglycerides, cholesterol, and related lipoproteins are major constituents of the lipid fraction of the human body, playing essential physiological roles such as cell membrane stability, energy storage, hormone and bile acid syntheses, dietary fat absorption and assembling, stress response, cell signaling, and calcium metabolism [1, 2]
Multiple genetic variants have been found to be associated with specific phenotypes and metabolic disorders, including dyslipidemia [6]
45 obesity-related single nucleotide polymorphisms (SNPs) were associated with circulating lipids (TC, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and TG)
Summary
Triglycerides, cholesterol, and related lipoproteins are major constituents of the lipid fraction of the human body, playing essential physiological roles such as cell membrane stability, energy storage, hormone and bile acid syntheses, dietary fat absorption and assembling, stress response, cell signaling, and calcium metabolism [1, 2]. Abnormalities in lipid metabolism may lead to the onset and development of several metabolic disorders, including cardiovascular disease features [3] In this context, elevated plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) have been associated with the risk of coronary heart disease, whereas high concentrations of high-density lipoprotein cholesterol (HDL-c) may exert a protective effect [4]. Growing scientific evidence suggests that geneenvironment interactions may influence plasma lipid phenotypes [5] Lifestyle factors such as diet, physical activity, alcohol drinking, and smoking have been recognized as important determinants of the blood lipid profile [5]. Some obesity-related genetic variants could help to predict blood lipid phenotypes
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