Lifestyle GenomicsPub Date : 2020-01-01Epub Date: 2020-10-26DOI: 10.1159/000507021
Bridget A Hannon, Caitlyn G Edwards, Sharon V Thompson, Sarah K Burke, Nicholas A Burd, Hannah D Holscher, Margarita Teran-Garcia, Naiman A Khan
{"title":"Genetic Variants in Lipid Metabolism Pathways Interact with Diet to Influence Blood Lipid Concentrations in Adults with Overweight and Obesity.","authors":"Bridget A Hannon, Caitlyn G Edwards, Sharon V Thompson, Sarah K Burke, Nicholas A Burd, Hannah D Holscher, Margarita Teran-Garcia, Naiman A Khan","doi":"10.1159/000507021","DOIUrl":"https://doi.org/10.1159/000507021","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 (>92 g/day) than those with a lower-fat diet (56 ± 3 vs. 46 ± 2 mg/dL, p = 0.033).</p><p><strong>Conclusions: </strong>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 ","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"155-163"},"PeriodicalIF":2.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000507021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40544541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lifestyle GenomicsPub Date : 2020-01-01Epub Date: 2019-12-10DOI: 10.1159/000503996
Michael T Paris
{"title":"Body Composition Analysis of Computed Tomography Scans in Clinical Populations: The Role of Deep Learning.","authors":"Michael T Paris","doi":"10.1159/000503996","DOIUrl":"https://doi.org/10.1159/000503996","url":null,"abstract":"<p><strong>Background: </strong>Body composition is increasingly being recognized as an important prognostic factor for health outcomes across cancer, liver cirrhosis, and critically ill patients. Computed tomography (CT) scans, when taken as part of routine care, provide an excellent opportunity to precisely measure the quantity and quality of skeletal muscle and adipose tissue. However, manual analysis of CT scans is costly and time-intensive, limiting the widespread adoption of CT-based measurements of body composition.</p><p><strong>Summary: </strong>Advances in deep learning have demonstrated excellent success in biomedical image analysis. Several recent publications have demonstrated excellent accuracy in comparison to human raters for the measurement of skeletal muscle, visceral adipose, and subcutaneous adipose tissue from the lumbar vertebrae region, indicating that analysis of body composition may be successfully automated using deep neural networks. Key Messages: The high accuracy and drastically improved speed of CT body composition analysis (<1 s/scan for neural networks vs. 15 min/scan for human analysis) suggest that neural networks may aid researchers and clinicians in better understanding the role of body composition in clinical populations by enabling cost-effective, large-scale research studies. As the role of body composition in clinical settings and the field of automated analysis advance, it will be critical to examine how clinicians interact with these systems and to evaluate whether these technologies are beneficial in improving treatment and health outcomes for patients.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"13 1","pages":"28-31"},"PeriodicalIF":2.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000503996","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37444986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lifestyle GenomicsPub Date : 2020-01-01Epub Date: 2019-12-17DOI: 10.1159/000504602
Anna Radziejewska, Agata Muzsik, Fermín I Milagro, J Alfredo Martínez, Agata Chmurzynska
{"title":"One-Carbon Metabolism and Nonalcoholic Fatty Liver Disease: The Crosstalk between Nutrients, Microbiota, and Genetics.","authors":"Anna Radziejewska, Agata Muzsik, Fermín I Milagro, J Alfredo Martínez, Agata Chmurzynska","doi":"10.1159/000504602","DOIUrl":"https://doi.org/10.1159/000504602","url":null,"abstract":"<p><p>The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Its etiology includes nutritional, genetic, and lifestyle factors. Several mechanisms may link one-carbon metabolism - the associated metabolic pathways of folate, methionine, and choline - to the onset of NAFLD. In this review, we attempted to assess how choline, folate, methionine, and betaine affect NAFLD development, mainly through their role in the secretion of very low-density lipoproteins (VLDL) from the liver. We also reviewed recent articles that have described the relation between microbiota metabolism and NAFLD progression. Moreover, we describe the effect of single-nucleotide polymorphisms (SNP) in genes related to one-carbon metabolism and disease prevalence. We additionally seek SNP identified by genome-wide associations that may increase the risk of this disease. Even though the evidence available is not entirely consistent, it seems that the concentrations of choline, methionine, folate, and betaine may affect the progression of NAFLD. Since there is no effective therapy for NAFLD, further investigations into the link between nutrition, gut microbiota, genetic factors, and NAFLD are still necessary, with a particular emphasis on methyl donors.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"13 2","pages":"53-63"},"PeriodicalIF":2.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000504602","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37465146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lifestyle GenomicsPub Date : 2020-01-01Epub Date: 2019-12-18DOI: 10.1159/000504603
Daiva E Nielsen, Yang Han, Catherine Paquet, Andre K Portella, Yu Ma, Laurette Dube
{"title":"Interaction of DRD2/ANKK1 Taq1A Genotype with in-Store Retail Food Environment Exposures on Diet Quality in a Cohort of Quebec Adults.","authors":"Daiva E Nielsen, Yang Han, Catherine Paquet, Andre K Portella, Yu Ma, Laurette Dube","doi":"10.1159/000504603","DOIUrl":"https://doi.org/10.1159/000504603","url":null,"abstract":"<p><strong>Background/aims: </strong>Gene-environment interactions may be relevant for nutrition outcomes. This study assessed the interaction between DRD2/ANKK1 Taq1A genotype and exposures to in-store retail food environment on diet quality.</p><p><strong>Methods: </strong>CARTaGENE biobank data (n = 3,532) were linked to provincial food retail data. The Canadian adaptation of the Healthy Eating Index 2010 (HEI-C) was calculated from food frequency questionnaires. Generalized linear models adjusted for sociodemographic factors, anthropometrics, and energy intake were used to assess interactions between the Taq1A variant and retail food measures.</p><p><strong>Results: </strong>A significant inverse interaction was observed between Taq1A and ice cream store displays on HEI-C score (estimate: -15.46 [95% confidence interval (CI): -24.83, -6.10], p = 0.0012) where, among allele carriers, increasing exposure to ice cream displays was associated with a lower HEI-C score as compared to allele carriers with a lower exposure. A significant positive interaction between Taq1A and price of vegetables was also observed, where, among allele carriers, increasing exposure to a higher price was associated with a higher HEI-C score compared to allele carriers with exposure to a lower price (estimate: 2.46 [95% CI: 0.78, 4.14], p = 0.0041). The opposite pattern was observed among non-carriers.</p><p><strong>Conclusions: </strong>DRD2/ANKK1 Taq1A is associated with adaptive responses to ice cream displays and vegetable prices, suggesting a differential susceptibility to retail environment food cues.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"13 2","pages":"74-83"},"PeriodicalIF":2.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000504603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37469629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lifestyle GenomicsPub Date : 2020-01-01Epub Date: 2020-07-13DOI: 10.1159/000508509
Luana Caroline Oliveira, Andrey Lucas Dias Barros, Angelica Beate Winter Boldt, Gabriel Adelman Cipolla
{"title":"Lack of Association between LCT_rs140433552*CA>del Indel Polymorphism and Lactose Intolerance in a Southern Brazilian Population.","authors":"Luana Caroline Oliveira, Andrey Lucas Dias Barros, Angelica Beate Winter Boldt, Gabriel Adelman Cipolla","doi":"10.1159/000508509","DOIUrl":"https://doi.org/10.1159/000508509","url":null,"abstract":"<p><strong>Background/aims: </strong>Polymorphisms in the enhancer of the lactase gene (LCT) are strongly associated with lactase persistence, but not always predictive of the phenotype. We investigated a possible association between the regulatory rs140433552*CA>del variant of LCT and lactose intolerance (LI).</p><p><strong>Methods: </strong>We genotyped 122 individuals for rs140433552 and rs4988235 (-13910*C>T).</p><p><strong>Results: </strong>Associations of rs140433552*CA>del with LI depend on -13910*C>T. Homozygous individuals for the C-CA haplotype, as well as C-CA+/C individuals, seem more likely to manifest LI (OR 3.33 [95% CI 1.32-8.35], p = 0.011, and OR 3.93 [95% CI 1.61-9.61], p = 0.003, respectively), while homozygous individuals for the T-CA haplotype seem more likely to be lactose tolerant (OR 0.04 [95% CI 0.002-0.70], p = 8 × 10-4).</p><p><strong>Conclusions: </strong>rs140433552*CA>del is not independently associated with LI.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"13 4","pages":"129-133"},"PeriodicalIF":2.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000508509","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38150025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Alpinia zerumbet and Its Potential Use as an Herbal Medication for Atherosclerosis: Mechanistic Insights from Cell and Rodent Studies.","authors":"Ting Xiao, Jiaoyan Huang, Xiaowei Wang, Linjing Wu, Xue Zhou, Feng Jiang, Zhiyong He, Qianqian Guo, Ling Tao, Xiangchun Shen","doi":"10.1159/000508818","DOIUrl":"https://doi.org/10.1159/000508818","url":null,"abstract":"<p><strong>Background/aims: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>A. zerumbet has potential functions and applications in the prevention of atherosclerosis, but further studies are required before clinical trials.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"13 5","pages":"138-145"},"PeriodicalIF":2.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000508818","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38342552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lifestyle GenomicsPub Date : 2020-01-01Epub Date: 2020-02-18DOI: 10.1159/000505749
Catherine A M Graham, Charles R Pedlar, Gary Hearne, Silvia Lorente-Cebrián, Pedro González-Muniesa, Yiannis Mavrommatis
{"title":"The Association of Parental Genetic, Lifestyle, and Social Determinants of Health with Offspring Overweight.","authors":"Catherine A M Graham, Charles R Pedlar, Gary Hearne, Silvia Lorente-Cebrián, Pedro González-Muniesa, Yiannis Mavrommatis","doi":"10.1159/000505749","DOIUrl":"https://doi.org/10.1159/000505749","url":null,"abstract":"<p><strong>Introduction: </strong>In the UK, the number of comorbidities seen in children has increased along with the worsening obesity rate. These comorbidities worsen into adulthood. Genome-wide association studies have highlighted single nucleotide polymorphisms associated with the weight status of adults and offspring individually. To date, in the UK, parental genetic, lifestyle, and social determinants of health have not been investigated alongside one another as influencers of offspring weight status. A comprehensive obesity prevention scheme would commence prior to conception and involve parental intervention including all known risk factors. This current study aims to identify the proportion of overweight that can be explained by known parental risk factors, including genetic, lifestyle, and social determinants of health with offspring weight status in the UK.</p><p><strong>Methods: </strong>A cross-sectional study was carried out on 123 parents. Parental and offspring anthropometric data and parental lifestyle and social determinants of health data were self-reported. Parental genetic data were collected by use of GeneFiX saliva collection vials and genotype were assessed for brain-derived neurotrophic factor (BDNF) gene rs6265, melanocortin 4 receptor (MC4R) gene rs17782313, transmembrane protein 18 (TMEM18) gene rs2867125, and serine/threonine-protein kinase (TNN13K) gene rs1514175. Associations were assessed between parental data and the weight status of offspring.</p><p><strong>Results: </strong>Maternal body mass index modestly predicted child weight status (p < 0.015; R2 = 0.15). More mothers of overweight children carried the MC4R rs17782313 risk allele (77.8%; p = 0.007) compared to mothers of normal-weight children. Additionally, fathers who were not Caucasian and parents who slept for <7 h/night had a larger percentage of overweight children when compared to their counterparts (p = 0.039; p = 0.014, respectively).</p><p><strong>Conclusion: </strong>Associations exist between the weight status of offspring based solely on parental genetic, lifestyle, and social determinants of health data. Further research is required to appropriately address future interventions based on genetic and lifestyle risk groups on a pre-parent cohort.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"13 2","pages":"99-106"},"PeriodicalIF":2.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000505749","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37652077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lifestyle GenomicsPub Date : 2020-01-01Epub Date: 2020-02-07DOI: 10.1159/000502773
Fang Cai, Yandi Liu, Dhanushka S Hettiarachichi, Fenglei Wang, Jie Li, Bruce Sunderland, Duo Li
{"title":"Ximenynic Acid Regulation of n-3 PUFA Content in Liver and Brain.","authors":"Fang Cai, Yandi Liu, Dhanushka S Hettiarachichi, Fenglei Wang, Jie Li, Bruce Sunderland, Duo Li","doi":"10.1159/000502773","DOIUrl":"https://doi.org/10.1159/000502773","url":null,"abstract":"<p><strong>Background/aims: </strong>Ximenynic acid is a rare conjugated enyne fatty acid found primarily in plants in the Santalaceae family. It has been reported that sandalwood seed oil (SWSO) affects fatty acid metabolism in animal studies; however, the effects of pure ximenynic acid remain unclear. The present study aimed to study the impact of SWSO and ximenynic acid on n-3 fatty acid metabolism in the liver and brain.</p><p><strong>Methods: </strong>Thirty C57BL/6 male mice aged 4 weeks were fed SWSO (1.0 mL/20 g bodyweight), olive oil (OO), or a combination of SWSO and OO (n = 10/group) for 8 weeks. Liver and brain fatty acid compositions were determined using gas chromatography. HepG2 cells were treated with up to 150 μM ximenynic acid and oleic acid for 48-72 h. The expression and abundance of genes and proteins relevant to n-3 fatty acid metabolism pathways were investigated.</p><p><strong>Results: </strong>The intake of SWSO in mice elevated the levels of total n-3 fatty acids and decreased total n-9 fatty acids in the liver (p < 0.05) compared with the OO group. In contrast, total n-3 fatty acids were significantly decreased in the brain (p < 0.05). HepG2 cells treated with ximenynic acid for 48 h showed significant reductions in n-9 fatty acids and docosahexaenoic acid (C22:6n-3) (p < 0.05) compared with HepG2 cells treated with oleic acid. In HepG2 cells, stearoyl-CoA desaturase (SCD) and fatty acid desaturase 2 (FADS2) gene expression, as well as FADS2 protein expression, were significantly down-regulated after a 72-h incubation with 150 μM of ximenynic acid compared with the vehicle (p < 0.05).</p><p><strong>Conclusion: </strong>Ximenynic acid may regulate fatty acid metabolism by suppressing the expression of key enzymes of lipid metabolism. In contrast, SWSO, which has a high level of C18:3n-3, positively affected n-3 fatty acid synthesis in mouse liver compared to pure ximenynic acid. We hypothesize that a high level of precursor C18:3n-3 in SWSO promotes the endogenous synthesis of C22:6n-3 despite the presence of ximenynic acid.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"13 2","pages":"64-73"},"PeriodicalIF":2.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000502773","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37625460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lifestyle GenomicsPub Date : 2020-01-01Epub Date: 2020-08-13DOI: 10.1159/000509663
Michael A Zulyniak, Harriett Fuller, Mark M Iles
{"title":"Investigation of the Causal Association between Long-Chain n-6 Polyunsaturated Fatty Acid Synthesis and the Risk of Type 2 Diabetes: A Mendelian Randomization Analysis.","authors":"Michael A Zulyniak, Harriett Fuller, Mark M Iles","doi":"10.1159/000509663","DOIUrl":"https://doi.org/10.1159/000509663","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Aim: </strong>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.</p><p><strong>Methods: </strong>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 < 10-8). After pruning, 1 variant (rs174547) on the FADS1 gene was retained.</p><p><strong>Results: </strong>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 <1%; p < 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.</p><p><strong>Conclusion: </strong>In a primarily white European population, LC n-6 PUFA synthesis is not a major contributor to T2D risk.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"13 5","pages":"146-153"},"PeriodicalIF":2.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000509663","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38269689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Abbasalizad Farhangi, M. Vajdi, L. Nikniaz, Zeinab Nikniaz
{"title":"Interaction between Vascular Endothelial Growth Factor-A (rs2010963) Gene Polymorphisms and Dietary Diversity Score on Cardiovascular Risk Factors in Patients with Metabolic Syndrome","authors":"M. Abbasalizad Farhangi, M. Vajdi, L. Nikniaz, Zeinab Nikniaz","doi":"10.1159/000503789","DOIUrl":"https://doi.org/10.1159/000503789","url":null,"abstract":"Background: The vascular endothelial growth factor-A (VEGFA) family of cytokines regulates proliferation, angiogenesis, and migration of endothelial cells, increases vascular permeability, and controls thrombogenicity. Recent studies have suggested that the VEGFA gene plays an important role in the pathogenesis of metabolic syndrome and its related disorders. Dietary diversity score (DDS) has also been shown to have potential favorable effects against features of metabolic syndrome. This study examined the interactions between +405 VEGFA C/G (rs2010963) polymorphism and DDS on the metabolic and biochemical profile of metabolic syndrome. Therefore, in the current study, we aimed to evaluate the interaction between DDS and VEGFA rs2010963 gene polymorphisms in modification of metabolic risk factors including serum lipids, blood pressure, serum adiponectin, and matrix metalloproteinase (MMP)-3 concentrations in patients with metabolic syndrome. Methods and Materials: In the current cross-sectional study, 254 patients with metabolic syndrome were recruited. Measurements of blood pressure, anthropometric parameters, and dietary intakes were performed and the DDS was calculated. Biochemical variables including serum adiponectin concentrations, lipid profile, serum glucose, and MMP-3 concentrations were measured by enzyme-linked immunosorbent assay method (ELISA) and enzymatic colorimetric methods. Determination of +405 C/G VEGFA gene polymorphisms was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: Patients in the lowest DDS quartile had higher insulin and homeostatic model assessment of insulin resistance (HOMA-IR), while patients in the highest DDS quartile had higher quantitative insulin check index (QUICKI; p < 0.05). Higher serum triglyceride and systolic blood pressure (SBP) values and lower serum adiponectin concentrations were also observed in lower DDS quartiles (p < 0.05). Patients with the CC genotype in the VEGFA rs2010963 polymorphism had significantly higher body mass index (BMI), fasting blood glucose, aspartate aminotransferase (AST), and alanine aminotransferase (ALT; p < 0.05) compared to patients with the other 2 genotypes. In lower quartiles of DDS, 30% of patients with metabolic syndrome had the GG genotype, while 30.4 and 30.8% of patients with metabolic syndrome in higher DDS quartiles had GC and CC genotypes, respectively (p = 0.04). Conclusion: Our study found lower insulin resistance, serum triglyceride, and SBP and higher adiponectin concentrations among patients with metabolic syndrome in highest quartiles of DDS. Moreover, patients with the CC genotype were more likely to have higher BMI, fasting blood glucose, AST, and ALT. This significant interaction gives a possible evidence of a VEGFA-DDS association that may be relevant to metabolic syndrome. Further studies are warranted to clarify the underlying mechanisms of these interactions.","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"13 1","pages":"1 - 10"},"PeriodicalIF":2.6,"publicationDate":"2019-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000503789","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47995457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}