Abstract: Introduction: Obesity results from an imbalance in the intake and expenditure of calories that leads to lifestyle-related diseases. Although genome-wide association studies (GWAS) have revealed many obesity-related genetic factors, the interactions of these factors and calorie intake remain unknown. This study aimed to investigate interactions between calorie intake and the polygenic risk score (PRS) of BMI. Methods: Three cohorts, i.e., from the Korea Association REsource (KARE; n = 8,736), CArdioVAscular Disease Association Study (CAVAS; n = 9,334), and Health EXAminee (HEXA; n = 28,445), were used for this study. BMI-related genetic loci were selected from previous GWAS. Two scores, PRS, and association (a)PRS, were used; the former was determined from 193 single-nucleotide polymorphisms (SNPs) from 5 GWAS datasets, and the latter from 62 SNPs (potentially associated) from 3 Korean cohorts (meta-analysis, p #x3c; 0.01). Results: PRS and aPRS were significantly associated with BMI in all 3 cohorts but did not exhibit a significant interaction with total calorie intake. Similar results were obtained for obesity. PRS and aPRS were significantly associated with obesity but did not show a significant interaction with total calorie intake. We further analyzed the interaction with protein, fat, and carbohydrate intake. The results were similar to those for total calorie intake, with PRS and aPRS found to not be associated with the interaction of any of the 3 nutrition components for either BMI or obesity. Discussion: The interaction of BMI PRS with calorie intake was investigated in 3 independent Korean cohorts (total n = 35,094) and no interactions were found between PRS and calorie intake for obesity. Lifestyle Genomics PubDate: Thu, 10 Dec 2020 10:43:02 +010
Abstract: Background: The phenotypic expression of a high-density lipoprotein (HDL) genetic risk score has been shown to depend upon whether the phenotype (HDL-cholesterol) is high or low relative to its distribution in the population (quantile-dependent expressivity). This may be due to the effects of genetic mutations on HDL-metabolism being concentration dependent. Method: The purpose of this article is to assess whether some previously reported HDL gene-lifestyle interactions could potentially be attributable to quantile-dependent expressivity. Summary:Seventy-three published examples of HDL gene-lifestyle interactions were interpreted from the perspective of quantile-dependent expressivity. These included interactive effects of diet, alcohol, physical activity, adiposity, and smoking with genetic variants associated with the ABCA1, ADH3, ANGPTL4, APOA1, APOA4, APOA5, APOC3, APOE, CETP, CLASP1, CYP7A1, GALNT2, LDLR, LHX1, LIPC, LIPG, LPL, MVK-MMAB, PLTP, PON1, PPARα, SIRT1, SNTA1,and UCP1genes. The selected examples showed larger genetic effect sizes for lifestyle conditions associated with higher vis-à-vis lower average HDL-cholesterol concentrations. This suggests these reported interactions could be the result of selecting subjects for conditions that differentiate high from low HDL-cholesterol (e.g., lean vs. overweight, active vs. sedentary, high-fat vs. high-carbohydrate diets, alcohol drinkers vs. abstainers, nonsmokers vs. smokers) producing larger versus smaller genetic effect sizes. Key Message: Quantile-dependent expressivity provides a potential explanation for some reported gene-lifestyle interactions for HDL-cholesterol. Although overall genetic heritability appears to be quantile specific, this may vary by genetic variant and environmental exposure. Lifestyle Genomics PubDate: Wed, 09 Dec 2020 09:36:56 +010
Abstract: Background: Even though excessive adipose tissue is related to chronic metabolic disturbances, not all subjects with excess weight (EW) display metabolic alterations, and not all normal-weight (NW) subjects have a metabolically healthy (MH) phenotype, probably due to gene-environment interactions. The aim of this study was to investigate the interaction effects of ADIPOQ and PPARG genetic variants in NW and EW individuals with different metabolic phenotypes. Methods: Data on 345 adults from western Mexico were analyzed. The individuals were classified into NW and EW groups according to body mass index, and were categorized as MH or metabolically unhealthy (MUH), considering homeostatic model assessment insulin resistance (HOMA-IR) and National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) cut-off points for glucose, triglycerides, high-density lipoprotein cholesterol, and blood pressure. Subjects with ≤1 altered parameter were classified as MH. The single nucleotide polymorphisms (SNPs) –11377C#x3e;G, –11391G#x3e;A, +45T#x3e;G, and +276G#x3e;T for ADIPOQ and Pro12Ala for PPARG were analyzed by allelic discrimination. High-molecular-weight adiponectin isoform levels were measured by ELISA. Results: Lower serum adiponectin levels were associated with the MUH phenotype in EW subjects. NW subjects with the GG or TG genotype for the +45T#x3e;G SNP had reduced odds of the MUH phenotype. Individuals who carried two copies of the GG haplotype at the –11391G#x3e;A and –11377C#x3e;G SNPs for ADIPOQ had lower serum adiponectin levels than those with zero copies. Conclusion: In this population, lower serum adiponectin levels were found in the EW-MUH phenotype, and no differences were observed between the NW-MH and the EW-MH phenotype. In addition, the +45T#x3e;G SNP was associated with reduced odds of the MUH phenotype. Lifestyle Genomics PubDate: Mon, 02 Nov 2020 14:12:00 +010
Abstract: Introduction: The effect of various types of dietary fat on cardiometabolic health continues to be debated, due in part to the high heterogeneity of results following clinical trials investigating the effects of saturated (SFA) and unsaturated fat intake. This variability may be due to genetic differences. Individuals with obesity are at an increased risk for adverse cardiometabolic health and dyslipidemia, and often present with the combined phenotype of elevated triglyceride (TG) and decreased high-density lipoprotein (HDL) cholesterol concentrations. Studying genetic variants relevant to lipid and lipoprotein metabolism can elucidate the mechanisms by which diet might interact with genotype to influence these phenotypes. The objective of this study was to determine relationships of genetic variation, dietary fat intake, and blood lipid concentrations in adults with overweight and obesity. Methods: Genomic DNA, blood lipid concentrations (HDL and TG), and 7-day diet records were obtained from 101 adults (25–45 years of age) with overweight or obesity. Resting energy expenditure (REE) was measured using indirect calorimetry and used to determine implausible intakes using a modified Goldberg method (kilocalories/REE). Genetic variants included 23 single-nucleotide polymorphisms (SNPs) from 15 genes in lipid metabolism pathways. Variants were analyzed with dietary fat intake (total fat, SFA, monounsaturated fat [MUFA], and polyunsaturated fat [PUFA]) via regression analyses. All models were adjusted for age, sex, ancestry, visceral adipose tissue mass, and total kilocalorie intake. The Bonferroni correction was applied for multiple comparisons. Results: Two interactions were detected for TG concentrations. Five gene-diet interactions were associated with HDL concentrations. There was a significant interaction detected between the rs5882 variant of cholesterol-esterase transfer protein (CETP) and MUFA intake to associate with TG concentrations (interaction p = 0.004, R2 = 0.306). Among carriers of the CETP-rs5882 major allele (G), TG concentrations were significantly lower in individuals consuming more than the median MUFA intake (31 g/day) than in those with an intake below the median. Total dietary fat intake interacted with the rs13702 polymorphism of lipoprotein lipase (LPL) to associate with HDL concentrations (interaction p = 0.041, R2 = 0.419), by which individuals with the risk allele (G) had significantly higher HDL concentrations when consuming a higher-fat diet (#x3e;92 g/day) than those with a lower-fat diet (56 ± 3 vs. 46 ± 2 mg/dL, p = 0.033). Conclusions: Interactions between dietary intake and genes in lipid metabolism pathways were found to be associated with blood lipid concentrations in adults with overweight and obesity. Fatty acid intake may not modulate blood lipid concentrations uniformly across all individuals. Additional research is needed to determine the biological causes of individual variability in response to dietary intake. Understanding the influence of nutrigenetic interactions on dyslipidemia can aid in the development and implementation of personalized dietary strategies to improve health. Lifestyle Genomics PubDate: Mon, 26 Oct 2020 07:56:44 +010
Abstract: Background: The role of adiponectin (ADIPOQ) polymorphisms in weight loss and serum lipid changes following different dietary interventions remain unclear. The Mediterranean dietary pattern has been associated with improved cardiovascular risk factors in different studies. Objective: Our aim was to analyze the effects of a hypocaloric diet with a Mediterranean dietary pattern on the metabolic response and adiposity parameters, taking into account the 712 G/A rs3774261 polymorphisms in ADIPOQ. Design: A population of 135 obese patients was enrolled. Anthropometric and serum parameters (lipid profile, insulin, homeostasis model assessment for insulin resistance [HOMA-IR], glucose, C-reactive protein [CRP], adiponectin, resistin, and leptin levels) were measured before and after the dietary intervention (12 weeks). All of the patients were genotyped for the rs3774261 polymorphism. Results: The genotype distribution of this population was 36 patients with AA (26.7%), 68 patients with AG (50.4%), and 31 patients with GG (22.9%). After the dietary intervention and in both genotypes, BMI, weight, fat mass, systolic blood pressure, waist circumference, glucose, insulin, HOMA-IR, and leptin levels all decreased. After the dietary intervention with secondary weight loss and in non-G-allele carriers (AA vs. AG+GG), total cholesterol (Δ = –15.7 ± 3.9 vs. –4.9 ± 2.9 mg/dL; p = 0.02), LDL cholesterol (Δ = –15.3 ± 3.8 vs. –1.7 ± 1.9 mg/dL; p = 0.01), triglyceride levels (Δ = –23.4 ± 5.6 vs. 2.3 ± 2.3 mg/dL; p = 0.01), and CRP (Δ = –1.1 ± 0.1 vs. –0.4 ± 0.2 mg/dL; p = 0.01) decreased. Adiponectin levels (Δ = 7.2 ± 2.1 vs. –0.4 ± 0.3 ng/dL; p = 0.02) increased. Notably, G-allele carriers did not show this improvement. Conclusion: Non-G-allele carriers of the ADIPOQ variant (rs3774261) showed significant improvement in serum levels of adiponectin, lipid profiles, and CRP in response to a hypocaloric diet with a Mediterranean dietary pattern. Lifestyle Genomics PubDate: Mon, 19 Oct 2020 11:22:57 +020
Abstract: Background: Lifestyle genomics (LGx) is a science that explores interactions between genetic variation, lifestyle components such as physical activity (PA), and subsequent health- and performance-related outcomes. The objective of this study was to determine whether an LGx intervention could motivate enhanced engagement in PA to a greater extent than a population-based intervention. Methods: In this pragmatic randomized controlled trial, participants received either the standard, population-based Group Lifestyle BalanceTM (GLB) program intervention or the GLB program in addition to the provision of LGx information and advice (GLB + LGx). Participants (n = 140) completed a 7-day PA recall at baseline, 3, 6, and 12 months. Data from the PA recalls were used to calculate metabolic equivalents (METs), a measure of energy expenditure. Statistical analyses included split plot analyses of covariance and binary logistic regression (generalized linear models). Differences in leisure time PA weekly METs, weekly minutes of moderate + high-intensity PA, and adherence to PA guidelines were compared between groups (GLB and GLB + LGx) across the 4 time points. Results: Weekly METs were significantly higher in the GLB + LGx group (1,114.7 ± 141.9; 95% CI 831.5–1,397.8) compared to the standard GLB group (621.6 ± 141.9 MET/week; 95% CI 338.4–904.8) at the 6-month follow-up (p = 0.01). All other results were non-significant. Conclusions: The provision of an LGx intervention resulted in a greater weekly leisure time PA energy expenditure after the 6-month follow-up. Future research should determine how this could be sustained over the long-term. Clinical Trial Registration: NCT03015012. Lifestyle Genomics PubDate: Thu, 01 Oct 2020 09:19:05 +020
Abstract: Background/Aims: Alpinia zerumbet (Pers.) Burtt. et Smith has been used as a flavor additive in food and a traditional medicine for centuries, especially in Guizhou Province, China, and it prolongs people’s lives with multiple beneficial effects. Thus, one of the aims of this review was to expound the chemical constituents of this plant, especially its fruits. Since cardiovascular diseases, including atherosclerosis, pose a health threat to humans, another aim was to expound the possible mechanisms of its potential use as an herbal medication for atherosclerosis. Methods: In this study, 10 reports are cited to expound the potential bioactive compounds. Moreover, 33 reports explain the antihypertensive and antiatherosclerotic effects of the plant by ameliorating inflammation and endothelial dysfunction, increasing vasodilation, improving hyperlipidemia, downgrading the glucose status, and working as an antioxidant. Results: A. zerumbetis rich in terpenes, essential oils, flavonoids, polyphenolics, and sterols. Pharmacological experiments showed that A. zerumbet has antioxidative and anti-inflammatory effects on the NF-κB signaling pathway and can ameliorate oxidative stress in the NOS-NO signaling pathway. Moreover, A. zerumbet demonstrates antihypertensive effects by accelerating vasorelaxant response and increasing 3T3-L1 intracellular cAMP, which has promising antiobesity properties, as well as hypolipidemic and anti-diabetic complication effects. Conclusions: A. zerumbet has potential functions and applications in the prevention of atherosclerosis, but further studies are required before clinical trials. Lifestyle Genomics PubDate: Thu, 03 Sep 2020 11:18:41 +020
Abstract: Background: Globally, 1 in 11 adults has diabetes mellitus, and most of these cases are type 2 diabetes (T2D). The risk of T2D is influenced by many factors, including diet. The synthesis of long-chain n-6 polyunsaturated fatty acids (LC n-6 PUFA) has been posited as a risk factor for T2D; however, its causal role is uncertain. Aim: To test the causal effect of LC n-6 PUFA synthesis on insulin resistance and transgenerational T2D risk in a large cohort of men and women. Methods: Two-sample mendelian randomization (MR) was conducted to evaluate the effect of low or high levels of LC n-6 PUFA synthesis on glycemia and development of T2D in the UK Biobank (n = 463,010) and Meta-Analysis of Glucose- and Insulin-Related Traits Consortium (MAGIC; n = 5,130) cohorts. The increased likelihood of a predisposition to low or high LC n-6 PUFA synthesis and the risk of T2D was also investigated using the participants’ siblings and parents. In MR-Base, 4 genetic variants associated with LC n-6 PUFA synthesis were found (p #x3c; 10–8). After pruning, 1 variant (rs174547) on the FADS1 gene was retained. Results: Lower LC n-6 PUFA synthesis and abundance (per % unit decrease) are associated with small reductions in the insulin disposition index (–0.038 ± 0.012 mM–1; p = 0.002) within MAGIC. In the UK Biobank, we report negligible effects of low n-6 PUFA synthesis on the odds of T2D (OR #x3c;1%; p #x3c; 0.05). Additionally, reduced LC n-6 PUFA synthesis does not appear to be a contributor to familial T2D risk. No significant association was observed between LC n-6 PUFA synthesis and BMI. Conclusion: In a primarily white European population, LC n-6 PUFA synthesis is not a major contributor to T2D risk. Lifestyle Genomics PubDate: Thu, 13 Aug 2020 15:21:13 +020
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