Abstract: Introduction: Obesity is a prevalent multifactorial disease whose main complication is dyslipidemia. Serum lipid levels also depend on genetic factors including the Taq1B variant of the CETP gene, which is suggested to be influenced by environmental factors and adiposity. Therefore, this study aimed to determine the effect of the Taq1B CETP variant on serum lipid levels associated with anthropometrical variables. Methods: 165 women from Western Mexico were enrolled in this cross-sectional study. Weight and body fat were measured by bioimpedance and waist circumference with a measuring tape. Serum lipid levels were determined by dry chemistry. The Taq1B CETP variant was analyzed by allelic discrimination. Results: Women with abdominal obesity and B1B2/B2B2 genotype had significantly higher total cholesterol levels (195.17 (185.95-204.39) vs 183 mg/dL (169.83-196.16), p = 0.007) and LDL (118.84 (110.65-127.03) vs 113.84 mg/dL (102.37-125.31), p = 0.037) than carriers of B1B1 genotype. Likewise, subjects with excessive adiposity and B1B2/B2B2 genotype showed significantly higher total cholesterol levels (195.05 (186.04-204.06) vs 182.40 mg/dL (169.03-195.76), p = 0.003) than those with B1B1 genotype. Discussion/Conclusion: Women with abdominal obesity or excessive adiposity, who are also carriers of the B1B2/B2B2 genotype have higher serum lipid levels than women with the B1B1 genotype.
Abstract: Introduction: Despite multiple studies which have considered the role of dietary acid load (DAL) or Apolipoprotein B (ApoB) EcoR1 polymorphism in diabetes, none have assessed their interplay effect on metabolic markers. Therefore, this study aimed to determine the interaction of EcoR1 and DAL on metabolic markers among adults with Type 2 diabetes mellitus (T2DM).Methods: 492 randomly selected individuals with T2DM were recruited for this cross-sectional study. Dietary intake was evaluated by a validated food frequency questionnaire. DAL was assessed as net-endogenous acid production (NEAP) and potential renal acid load (PRAL). Real-time-PCR was used to genotype EcoR1. Metabolic markers were also assessed. The interaction effect of the polymorphism and DAL indexes was analyzed by analysis of covariance (ANCOVA). Result: The frequency of EcoR1 genotypes was not different between dyslipidemic and normolipidemic participants (P>0.05). Among participants with dyslipidemia, those with the GG genotype and who consumed a higher level of NEAP had higher body mass index (BMI) (p=0.03) and waist circumference (WC; p =0.02). Moreover, triglyceride (TG) concentration (P=0.007), the LDL/HDL ratio (P=0.03) and the TG/HDL (P=0.03) ratio were significantly higher in A allele carriers with higher than the median intake of NEAP, in comparison with GG homozygotes. Finally, GA/AA carriers who had a higher intake of PRAL had a higher TG concentration (P=0.006) and TG/HDL ratio (P=0.01) compared to lower median intake in the dyslipidemia group. Discussion/Conclusion: In the dyslipidemic group, there was a higher TG concentration among individuals with the GA/AA genotype and a higher intake of NEAP/ PRAL. Also, in this group, a higher intake of NEAP may be considered as a risk factor for increased levels of BMI and WC among participants with the GG genotype.
Abstract: Background: Our daily intake of food provides nutrients for the maintenance of health, growth and development. The field of nutrigenomics aims to link dietary intake/nutrients to changes in epigenetic status and gene expression. Summary: Although the relationship between our diet and our genes in under intense investigation, there is still as significant aspect of our genome that have received little attention with regards to this. In the past 15 years the importance of genome organization has become increasingly evident, with research identifying small scale local changes to large segments of the genome dynamically repositioning within the nucleus in response to/or mediating change in gene expression. The discovery of these dynamic processes and organization maybe as significant as dynamic plate tectonics is to geology, there is little information tying genome organization to specific nutrients or dietary intake. Key Messages: Here we detail key principles of genome organization and structure, with emphasis on genome folding and organization, and link how these contribute to our future understand of nutrigenomics.
Abstract: IntroductionAlthough investigations into the emerging field of nutrigenomics are relatively limited and more research in this field is required, experts agree that there is potential for it to be incorporated into health care practice. If health care professionals can promote healthy dietary behaviour based on nutrigenomic testing, it can assist in addressing the health consequences of poor diet and lightening the strain on the South African health care system.MethodsRegistered dietitians (RDs) and general practitioners (GPs) registered with the Health Professions Council of South Africa (HPCSA) who obtained their qualification in South Africa (SA), were eligible to participate in this cross-sectional study. Participants were identified using convenience and snowball sampling. A self-administered electronic survey using EvaSys Software® was completed by those that agreed to participate.ResultsNearly all RDs (97.3%), but less than a third of GPs (30.4%), had heard of the term nutrigenomics. Approximately three-quarters of RDs (74.7%) and GPs (73.9%) had or would personally consider undergoing genetic testing. More than forty percent (43.5%) of RDs ranked direct-to-consumer (DTC) genetic testing companies as the most equipped, while 31.8% of GPs ranked RDs as the most equipped to provide patients with nutrigenomic services.Both RDs and GPs ranked similar reasons as ‘strongly agree’ for why consumers were motivated to make use of nutrigenomic services, which included ‘motivated by a desire to prevent or manage disease’ (56.7%), ‘prevent a disease based on family history’ (65.9%), ‘control health outcomes based on family history’ (54.9%), and ‘improve overall health-related quality of life’ (48.6%). Cost concerns were reported as the greatest barrier to implementing nutrigenomic services (75.7%). Other barriers included confidentiality issues (47.8%) and moral concerns (37.3%). Greater individualisation of diet prescription (66.5%), stronger foundations for nutrition recommendations (62.4%), and dietary prescriptions that would manage or prevent certain diseases more effectively (59.0%) were all perceived as benefits of including nutrigenomics in practice.Discussion/ConclusionThis study identified perceived consumer motivators and barriers that might affect the willingness to seek nutrigenomic services in SA. In addition, the need for more nutrigenomic training opportunities, including the planning of personalised diets based on genetic testing results and interpretation of results was confirmed. However, both RDs and GPs felt that the emerging field of nutrigenomics needs further development before it can be applied effectively in routine private and public health care in SA.
Abstract: Introduction: The prevalence of colon cancer remains high across the world. The early diagnosis of colon cancer is challenging. Moreover, patients with colon cancer frequently suffer from poor prognoses. Methods: Differentially expressed genes (DEGs) in colon cancer were acquired based on TCGA-COAD dataset screening. DEGs were input into the Connectivity Map (CMap) database to screen small molecule compounds with the potential to reverse colon cancer pathological function. Glycitein ranked first among the screened small-molecule compounds. We downloaded the main targets of glycitein from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database and constructed protein-protein interaction (PPI) networks of those which were closely related to targets by the Search Tool for the Retrieval of Interaction Gene/Proteins (STRING). Five potential targets of glycitein for treating colon cancer were identified (CCNA2, ESR1, ESR2, MAPK14, and PTGS2). These targets were used as seeds for random walk with restart (RWR) analysis of PPI networks. Then, the interaction network of glycitein-colon cancer-related genes was constructed based on the top 50 genes in affinity coefficients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the potential genes targeted by glycitein in colon cancer treatment and those that were closely bound up with targets. Results: GO analysis demonstrated that the enrichment of these genes was primarily discovered in biological functions including regulation of fibroblast proliferation, response to oxygen levels, and epithelial cell proliferation. The KEGG analysis results illustrated that the signaling pathways where these genes were mostly involved consisted of the mitogen-activated protein kinase signaling pathway, the phosphatidylinositol-3-kinase-Akt signaling pathway, and the p53 signaling pathway. Finally, stable binding of glycitein to five potential targets in colon cancer was verified by molecular docking. Conclusion: This study elucidated the key targets and main pathways of glycitein on the basis of network pharmacology and preliminarily analyzed molecular mechanisms in the treatment of colon cancer. A scientific basis is provided for glycitein application in treating colon cancer. Lifestyle Genomics PubDate: Fri, 30 Sep 2022 11:38:11 +020
Abstract: Introduction: “Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., mean platelet volume, MPV) is high or low relative to its distribution. Methods: Offspring-parent regression slopes (βOP) were estimated by quantile regression, from which quantile-specific heritabilities (h2) were calculated (h2 = 2βOP/[1 + rspouse]) for blood cell phenotypes in 3,929 parent-offspring pairs from the Framingham Heart Study. Results: Quantile-specific h2 (±SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted MPV distribution (plinear = 0.0001): 0.48 ± 0.09 at the 10th, 0.53 ± 0.04 at the 25th, 0.70 ± 0.06 at the 50th, 0.74 ± 0.06 at the 75th, and 0.90 ± 0.12 at the 90th percentile. Quantile-specific h2 also increased with increasing percentiles of the offspring’s white blood cell (WBC, plinear = 0.002), monocyte (plinear = 0.01), and eosinophil distributions (plinear = 0.0005). In contrast, heritibilities of red blood cell (RBC) count, hematocrit (HCT), and hemoglobin (HGB) showed little evidence of quantile dependence. Quantile-dependent expressivity is consistent with gene-environment interactions reported by others, including (1) greater increases in WBC and PLT concentrations in subjects who are glutathione-S-transferase Mu1 (GSTM1) null homozygotes than GSTM1 sufficient when exposed to endotoxin; (2) significantly higher WBC count in AA homozygotes than carriers of the G-allele of the glutathione S-transferase P1 (GSTP1) rs1695 polymorphism at low but not high benzene exposure in shoe factory workers; (3) higher WBC counts in TT homozygotes than C-allele carriers of the interleukin-1β (IL1B) c.315C#x3e;T polymorphism after undergoing surgery for infective endocarditis but not before surgery. Discussion/Conclusion: Quantile-dependent expressivity may explain several purported gene-environment interactions involving blood cell phenotypes. Lifestyle Genomics 2022;15:111–123 PubDate: Thu, 22 Sep 2022 07:46:21 +020
Abstract: Introduction: The fat mass and obesity-associated gene (FTO) is largely/primarily expressed in the hypothalamus. It plays a role in energy balance, regulation of food intake, and adipogenesis. According to metabolic phenotypes, studies have associated the FTO rs9939609 variant with body mass index (BMI), body fat mass, and dietary intake but not with serum lipids. This study aimed to analyze the association of the FTO rs9939609 variant with serum lipids in Mexican adults with different metabolic phenotypes. Methods: We included 306 subjects aged 18–65 years, classified as normal weight or excess weight (EW) according to their BMI. EW included BMI from 25 to 39.9 kg/m2. Participants were classified into two metabolic phenotypes: metabolically healthy/metabolically unhealthy (MH/MUH). We use the homeostatic model assessment of insulin resistance and NCEP-ATP III cutoffs for glucose, triglycerides, high-density lipoprotein, and blood pressure. Subjects with ≥2 altered parameters were classified as MUH. The variant was determined by allelic discrimination with TaqMan® probes. Results: In subjects with the A allele, significantly higher total cholesterol and low-density-lipoprotein cholesterol were found (p #x3c; 0.05). Furthermore, subjects with EW-MH and the AA or AT genotype had a significantly higher odds ratio for hypercholesterolemia (odds ratio 4.48, 95% confidence interval: 1.48–13.59, p = 0.008). Conclusion: The FTO rs9939609 variant may influence serum lipid concentrations, increasing the risk of hypercholesterolemia. Lifestyle Genomics 2022;15:131–138 PubDate: Wed, 21 Sep 2022 12:13:19 +020
Abstract: Introduction: In mammals, circadian rhythms regulate many behavioral and physiological processes. Genetic and epidemiological studies have shown that dysregulation of the circadian rhythm induces chronic metabolic diseases, such as obesity, diabetes, and dyslipidemia. We aimed to know the interactions of genetic variations of seven core circadian clock genes with lifestyle factors on the determination of metabolic parameters. Methods: We have analyzed the impacts of genotype of seven core circadian clock genes (i.e., CLOCK, BMAL1, PER1, PER2, PER3, CRY1, and CRY2) and lifestyle factors (i.e., physical activity and sleep duration) in 575 Japanese males on the determination of metabolic parameters (i.e., body mass index [BMI], serum glucose, glycated hemoglobin [HbA1c], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C] levels). Results: We have detected the associations between genotypes of PER3 and serum HbA1c level and genotypes of CRY1 and serum LDL-C level. Additionally, the interactions of the genotypes of PER1 and PER3 with physical activity for determining BMI, the genotypes of CLOCK with physical activity for determining serum HbA1c levels were observed. Furthermore, for determining serum HDL-C levels, the interactions of the genotypes of CRY2 with physical activity or sleep duration were observed. Discussion/Conclusion: Our findings indicate that the interactions of genotypes for core circadian clock genes and lifestyle factors (i.e., physical activity and sleep duration) are important for determining metabolic parameters. Lifestyle Genomics 2022;15:124–130 PubDate: Tue, 13 Sep 2022 08:28:29 +020
Abstract: Background: Arachidonic acid (ARA) is associated with colorectal cancer (CRC), a major public health concern. However, it is uncertain if ARA contributes to the development of colorectal polyps which are pre-malignant precursors of CRC. Objective: The study aimed to investigate the association between lifelong exposure to elevated ARA and colorectal polyp incidence. Methods: Summary-level GWAS data from European, Singaporean, and Chinese cohorts (n = 10,171) identified 4 single-nucleotide polymorphisms (SNPs) associated with blood ARA levels (p #x3c; 5 × 10−8). After pruning, 1 SNP was retained (rs174547; p = 3.0 × 10−971) for 2-stage Mendelian randomization. Results: No association between ARA and colorectal polyp incidence was observed (OR = 1.00; 95% CI: 0.99, 1.00; p value = 0.50) within the UK Biobank (1,391 cases; 462,933 total). Conclusions: Blood levels of ARA do not associate with colorectal polyp incidence in a general healthy population. Although not providing direct evidence, this work supports the contention that downstream lipid mediators, such as PGE2 rather than ARA itself, are key for polyp formation during early-stage colorectal carcinogenesis. Lifestyle Genomics 2022;15:107–110 PubDate: Thu, 11 Aug 2022 11:31:11 +020
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