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      Single Nucleotide Polymorphisms Related to Lipoprotein Metabolism Are Associated with Blood Lipid Changes following Regular Avocado Intake in a Randomized Control Trial among Adults with Overweight and Obesity

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          ABSTRACT

          Background

          Avocados are rich in unsaturated fat and fiber; clinical trials have investigated their effects on metabolic disease. There is high variability in individual changes following avocado consumption, which may be in part due to individual genetic differences.

          Objective

          Secondary analyses of the Persea americana for Total Health (PATH) Study were used to examine how single nucleotide polymorphisms (SNPs) impact blood lipid changes following a daily meal containing avocado compared with control.

          Methods

          Adults (n = 115, 37% male) aged 25–45 y with overweight and obesity were randomly assigned to receive a daily isocaloric meal with (intervention) or without (control) a standardized amount (males: 175 g; females: 140 g) of avocado for 12 wk. Control meals were higher in saturated fat (17% of energy compared with 7%) and lower in fiber (4 g compared with 16 g) than intervention meals. Whole venous blood was taken at baseline and 12 wk to determine total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglyceride (TG) concentrations. Seventeen SNPs in 10 genes related to lipoprotein metabolism were genotyped. Effects of SNP, diet, and SNP–diet interactions were determined using general linear models.

          Results

          No group-by-time effects were detected for changes in TC (P = 0.96), HDL cholesterol (P = 0.28), or TG (P = 0.06) over 12 wk. Three SNP–diet interactions were associated with final TC concentrations: ANGPTL3-rs10889337 (P = 0.01), ANGPTL4-rs2278236 (P = 0.02), and CD36-rs10499859 (P = 0.01). SNPs in GCKR and LPL were associated with TC changes (P = 0.01). The interaction between GCKR-rs1260326 and diet was such that C-homozygotes receiving avocado (n = 23) had final TC concentrations that were significantly lower than the C-homozygotes in the control group (n = 20) (P = 0.02).

          Conclusions

          Results from these exploratory analyses indicate that avocado consumption may help manage dyslipidemia in adults with overweight and obesity; however, effectiveness may differ by genetic profile. Understanding the role of genetic variation in variability following dietary intervention can potentially inform personalized nutrition recommendations.

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          Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study.

          Caroline S. Fox, Joseph Massaro, Udo Hoffmann … (2007)
          Visceral adipose tissue (VAT) compartments may confer increased metabolic risk. The incremental utility of measuring both visceral and subcutaneous abdominal adipose tissue (SAT) in association with metabolic risk factors and underlying heritability has not been well described in a population-based setting. Participants (n=3001) were drawn from the Framingham Heart Study (48% women; mean age, 50 years), were free of clinical cardiovascular disease, and underwent multidetector computed tomography assessment of SAT and VAT volumes between 2002 and 2005. Metabolic risk factors were examined in relation to increments of SAT and VAT after multivariable adjustment. Heritability was calculated using variance-components analysis. Among both women and men, SAT and VAT were significantly associated with blood pressure, fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol and with increased odds of hypertension, impaired fasting glucose, diabetes mellitus, and metabolic syndrome (P range < 0.01). In women, relations between VAT and risk factors were consistently stronger than in men. However, VAT was more strongly correlated with most metabolic risk factors than was SAT. For example, among women and men, both SAT and VAT were associated with increased odds of metabolic syndrome. In women, the odds ratio (OR) of metabolic syndrome per 1-standard deviation increase in VAT (OR, 4.7) was stronger than that for SAT (OR, 3.0; P for difference between SAT and VAT < 0.0001); similar differences were noted for men (OR for VAT, 4.2; OR for SAT, 2.5). Furthermore, VAT but not SAT contributed significantly to risk factor variation after adjustment for body mass index and waist circumference (P < or = 0.01). Among overweight and obese individuals, the prevalence of hypertension, impaired fasting glucose, and metabolic syndrome increased linearly and significantly across increasing VAT quartiles. Heritability values for SAT and VAT were 57% and 36%, respectively. Although both SAT and VAT are correlated with metabolic risk factors, VAT remains more strongly associated with an adverse metabolic risk profile even after accounting for standard anthropometric indexes. Our findings are consistent with the hypothesized role of visceral fat as a unique, pathogenic fat depot. Measurement of VAT may provide a more complete understanding of metabolic risk associated with variation in fat distribution.
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            Discovery and Refinement of Loci Associated with Lipid Levels

            Cristen Willer, Ellen M. Schmidt, Sebanti Sengupta … (2014)
            Low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and total cholesterol are heritable, modifiable, risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,578 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5×10−8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian, and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipids are often associated with cardiovascular and metabolic traits including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio, and body mass index. Our results illustrate the value of genetic data from individuals of diverse ancestries and provide insights into biological mechanisms regulating blood lipids to guide future genetic, biological, and therapeutic research.
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              Biological, Clinical, and Population Relevance of 95 Loci for Blood Lipids

              Tanya M. Teslovich, Kiran Musunuru, Albert V. Smith … (2010)
              Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with serum lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 × 10-8), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (e.g., CYP7A1, NPC1L1, and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and impact lipid traits in three non-European populations (East Asians, South Asians, and African Americans). Our results identify several novel loci associated with serum lipids that are also associated with CAD. Finally, we validated three of the novel genes—GALNT2, PPP1R3B, and TTC39B—with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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                Author and article information

                Journal
                Title: The Journal of Nutrition
                Publisher: Oxford University Press (OUP)
                ISSN (Print): 0022-3166
                ISSN (Electronic): 1541-6100
                Publication date Created: June 2020
                Publication date Created: June 01 2020
                Publication date Created: March 20 2020
                Publication date Other: June 2020
                Publication date (Print): June 01 2020
                Publication date (Electronic): March 20 2020
                Volume: 150
                Issue: 6
                Pages: 1379-1387
                Affiliations
                [1 ]Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
                [2 ]Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, USA
                [3 ]Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, USA
                [4 ]Department of Human Development and Family Studies, University of Illinois at Urbana-Champaign, Urbana, IL, USA
                Article
                DOI: 10.1093/jn/nxaa054
                PubMed ID: 32195538
                SO-VID: 2919db99-756a-4eb6-88b6-0fe135e7e3a6
                Copyright © © 2020
                License:

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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