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Inverse Association Between Serum 25-Hydroxyvitamin D and Nonalcoholic Fatty Liver Disease.
Yuan, S, Larsson, SC
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2023;21(2):398-405.e4
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The prevalence of non-alcoholic fatty liver disease (NAFLD) is projected to increase due to the obesity epidemic, rise in diabetes prevalence, and other factors. An inverse association between serum 25-hydroxyvitamin D [S-25(OH)D], a clinical marker of vitamin D status, and NAFLD has been observed in several cross-sectional and case-control studies. The aim of this study was to determine the association between S-25(OH)D and NAFLD. This study is a 2-sample Mendelian randomisation study based on summary-level data of genome-wide association analyses on S-25(OH)D levels, NAFLD, and liver enzymes. Results show an inverse genetic correlation of S-25(OH)D with NAFLD and certain liver enzymes and an inverse association of genetically predicted S-25(OH)D with risk of NAFLD in European individuals. Authors conclude that vitamin D may play a role in NAFLD prevention. However, further studies are needed in order to confirm the causal effect of NAFLD on lowering S-25(OH)D levels.
Abstract
BACKGROUND & AIMS Serum 25-hydroxyvitamin D [S-25(OH)D] and nonalcoholic fatty liver disease (NAFLD) are correlated in many observational studies, whereas the causality of this association is uncertain, especially in European populations. We conducted a bidirectional Mendelian randomization study to determine the association between S-25(OH)D and NAFLD. METHODS Seven and 6 independent genetic variants associated with S-25(OH)D and NAFLD at the genome-wide-significance level, respectively, were selected as instrumental variables. Summary-level data for S-25(OH)D were obtained from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits consortium including 79,366 individuals. Summary-level data for NAFLD were available from a genome-wide association meta-analysis (1483 cases and 17,781 controls), the FinnGen consortium (894 cases and 217,898 controls), and the UK Biobank study (275 cases and 360,919 controls). Summary-level data for 4 liver enzymes were obtained from the UK Biobank. RESULTS There were genetic correlations of S-25(OH)D with NAFLD and certain liver enzymes. Genetically predicted higher levels of S-25(OH)D were consistently associated with a decreased risk of NAFLD in the 3 sources. For a 1-SD increase in genetically predicted S-25(OH)D levels, the combined odds ratio of NAFLD was 0.78 (95% confidence interval [CI], 0.69 to 0.89). Genetically predicted higher levels of S-25(OH)D showed a borderline association with aspartate aminotransferase levels (change -1.17; 95% CI, -1.36 to 0.01). Genetic predisposition to NAFLD was not associated with S-25(OH)D (change 0.13; 95% CI, -1.26 to 0.53). CONCLUSIONS Our findings have clinical implications as they suggest that increased vitamin D levels may play a role in NAFLD prevention in European populations.
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Genomics in Personalized Nutrition: Can You "Eat for Your Genes"?
Mullins, VA, Bresette, W, Johnstone, L, Hallmark, B, Chilton, FH
Nutrients. 2020;12(10)
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Genetics may have a huge influence on how nutrients are processed within the body, challenging the one-size-fits-all dietary approach and highlighting the possible need for personalised nutrition based on genetics. There are a growing number of companies that offer genetic nutritional testing, however the science behind this is still in its infancy. This review of 130 papers aimed to discuss the role of genetics in nutrition and the possibility for precision nutrition. The paper stated that dietary components, especially those found in the modern Western diet (WD), may detrimentally interact with genetics. Overconsumption of certain nutrients, changes in nutrient exposure throughout history and the ability of certain nutrients to make small genetic changes are all ways that genetics and diet can interact. Therefore, understanding how an individual’s genetics have been and continue to be affected by diet may ensure effective nutrition recommendations. Ethical implications should be considered prior to testing and whether results will motivate or dissuade an individual to make dietary changes assessed. It was concluded that personalised nutrition recommendations in the future will rely upon understanding an individual’s genetics, however current research has a limited understanding of the numerous diet-genetic interactions. This paper could be used by healthcare professionals to evaluate the need for genetic testing to make personalised recommendations.
Abstract
Genome-wide single nucleotide polymorphism (SNP) data are now quickly and inexpensively acquired, raising the prospect of creating personalized dietary recommendations based on an individual's genetic variability at multiple SNPs. However, relatively little is known about most specific gene-diet interactions, and many molecular and clinical phenotypes of interest (e.g., body mass index [BMI]) involve multiple genes. In this review, we discuss direct to consumer genetic testing (DTC-GT) and the current potential for precision nutrition based on an individual's genetic data. We review important issues such as dietary exposure and genetic architecture addressing the concepts of penetrance, pleiotropy, epistasis, polygenicity, and epigenetics. More specifically, we discuss how they complicate using genotypic data to predict phenotypes as well as response to dietary interventions. Then, several examples (including caffeine sensitivity, alcohol dependence, non-alcoholic fatty liver disease, obesity/appetite, cardiovascular, Alzheimer's disease, folate metabolism, long-chain fatty acid biosynthesis, and vitamin D metabolism) are provided illustrating how genotypic information could be used to inform nutritional recommendations. We conclude by examining ethical considerations and practical applications for using genetic information to inform dietary choices and the future role genetics may play in adopting changes beyond population-wide healthy eating guidelines.
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Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.
Patrick, RP
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019;33(2):1554-1564
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Alzheimer’s disease (AD) is a neurodegenerative disorder characterised by progressive memory loss, spatial disorientation, cognitive impairment and behavioural changes. Ageing is the main risk factor for AD, with approximately one-third of Americans over the age of 85 being affected by the condition. The APOE gene provides instructions for making the apolipoprotein E family of proteins that are involved in fat metabolism and cholesterol transport. There are three different variants of this gene, one inherited from each parent. The variant called APOE4 is thought to increase AD risk from 2-3-fold (one inherited copy) to as much as 15-fold (two inherited copies), compared to individuals who do not carry this variant. The omega-3 oil docosahexaenoic acid (DHA) is an essential fatty acid, which comprises approximately 30% of the fats found in the human brain. Low levels of DHA in the brain increase the risk of developing AD, while normal and high levels may prevent the condition and ameliorate symptoms. This review paper brings together several lines of evidence on why individuals with the APOE4 gene variant don’t respond well to DHA supplementation but experience positive effects from dietary intake of DHA. The author suggests that this is due to the different forms of DHA found in dietary and supplemental sources. Some of the DHA present in fish and seafood is in phospholipid form, which is metabolised into lysophosphatidylcholine DHA (DHA-lysoPC) in the body. In contrast, fish oil supplements contain no DHA in phospholipid form, but in other forms that are mostly metabolised to free DHA. This paper puts forward an argument that, due to the breakdown of the integrity of the blood-brain barrier, APOE4 carriers have impaired brain transport of free DHA but not DHA-lysoPC. The author concludes that dietary sources that contain high amounts of DHA in phospholipid form, such as fish and fish roe may help increase plasma levels of DHA-lysoPC, which may be better transported to the brains of APOE4 carriers. She also highlights the pressing need for future clinical trials to evaluate the effects of omega-3 oils in phospholipid form on the cognitive function of APOE4 carriers with AD.
Abstract
Dietary and supplemental intake of the ω-3 fatty acid docosahexaenoic acid (DHA) reduces risk of Alzheimer's disease (AD) and ameliorates symptoms. The apolipoprotein E ( APOE) 4 allele is the strongest risk factor for sporadic AD, exclusive of age. APOE4 carriers respond well to the DHA present in fish but do not respond as well to dietary supplements. The mechanisms behind this varied response remain unknown. I posit that the difference is that fish contain DHA in phospholipid form, whereas fish oil supplements do not. This influences whether DHA is metabolized to nonesterified DHA (free DHA) or a phospholipid form called lysophosphatidylcholine DHA (DHA-lysoPC). Free DHA is transported across the outer membrane leaflet of the blood-brain barrier (BBB) via passive diffusion, and DHA-lysoPC is transported across the inner membrane leaflet of the BBB via the major facilitator superfamily domain-containing protein 2A. I propose that APOE4 carriers have impaired brain transport of free DHA but not of DHA-lysoPC, as a consequence of a breakdown in the outer membrane leaflet of the BBB, putting them at increased risk for AD. Dietary sources of DHA in phospholipid form may provide a means to increase plasma levels of DHA-lysoPC, thereby decreasing the risk of AD.-Patrick, R. P. Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.
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Starch Digestion-Related Amylase Genetic Variant Affects 2-Year Changes in Adiposity in Response to Weight-Loss Diets: The POUNDS Lost Trial.
Heianza, Y, Sun, D, Wang, T, Huang, T, Bray, GA, Sacks, FM, Qi, L
Diabetes. 2017;66(9):2416-2423
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Salivary and pancreatic amylases are responsible for the digestion of starchy foods. Specific genes that encode these amylases control both the activity and amount produced. While increasing evidence suggests the AMY1 gene is associated with obesity, existing results have not been conclusive. The aim of this study was to investigate whether genetic variations involved in starch metabolism are associated with long-term changes in adiposity among 692 overweight and obese individuals. Participants were randomly assigned to diets varying in macronutrient content for two years. Anthropometric measurements were recorded at baseline and every six months and blood samples were taken at baseline, 6 and 24 months. This study found the AMY1-AMY2 rs11185098 genotype to be associated with higher amylase activity, as well as reductions in body weight and waist circumference. Based on these results, the authors conclude overweight and obese individuals carrying this genotype may experience greater loss of adiposity during weight-loss interventions.
Abstract
Salivary and pancreatic amylases (encoded by AMY1 and AMY2 genes, respectively) are responsible for digesting starchy foods. AMY1 and AMY2 show copy number variations that affect differences in amylase amount and activity, and AMY1 copies have been associated with adiposity. We investigated whether genetic variants determining amylase gene copies are associated with 2-year changes in adiposity among 692 overweight and obese individuals who were randomly assigned to diets varying in macronutrient content. We found that changes in body weight (BW) and waist circumference (WC) were significantly different according to the AMY1-AMY2 rs11185098 genotype. Individuals carrying the A allele (indicating higher amylase amount and activity) showed a greater reduction in BW and WC at 6, 12, 18, and 24 months than those without the A allele (P < 0.05 for all). The association was stronger for long-term changes compared with short-term changes of these outcomes. The genetic effects on these outcomes did not significantly differ across diet groups. In conclusion, the genetic variant determining starch metabolism influences the response to weight-loss dietary intervention. Overweight and obese individuals carrying the AMY1-AMY2 rs11185098 genotype associated with higher amylase activity may have greater loss of adiposity during low-calorie diet interventions.
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Association Between Single Gene Polymorphisms and Bone Biomarkers and Response to Calcium and Vitamin D Supplementation in Young Adults Undergoing Military Training.
Gaffney-Stomberg, E, Lutz, LJ, Shcherbina, A, Ricke, DO, Petrovick, M, Cropper, TL, Cable, SJ, McClung, JP
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2017;32(3):498-507
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The risk of stress fracture is increased in initial military training (IMT) largely because of unaccustomed activity, resulting in a change in calcium and vitamin D levels. Genetic polymorphisms are variations in a gene that affect the level of gene expression, and bone metabolism and absorption is impacted by this. The primary aim of this randomised, double-blind, placebo controlled trial was to determine whether genes related to Calcium and vitamin D were associated with markers of bone metabolism in 748 young adults entering military training. Participants were randomised to consume bars between meals that were either supplemented with Calcium and vitamin D or placebo that were matched in taste and appearance. Fasting blood samples were taken before and after the 7- to 9-week IMT programme to assess circulating biomarkers and genes. This study found that genetic polymorphisms related to Calcium and vitamin D were associated with vitamin D status and markers of bone metabolism. It also found that genes could predict change in vitamin D absorption levels. Based on these results, the authors conclude this study provides novel insight that helps further understanding between genetics, environment and bone metabolism.
Abstract
Initial military training (IMT) is associated with increased stress fracture risk. In prior studies, supplemental calcium (Ca) and vitamin D provided daily throughout IMT reduced stress fracture incidence, suppressed parathyroid hormone (PTH), and improved measures of bone health compared with placebo. Data were analyzed from a randomized, double-blind, placebo-controlled trial to determine whether single-nucleotide polymorphisms (SNPs) in Ca and vitamin D-related genes were associated with circulating biomarkers of bone metabolism in young adults entering IMT, and whether responses to Ca and vitamin D supplementation were modulated by genotype. Associations between SNPs, including vitamin D receptor (VDR), vitamin D binding protein (DBP), and 1-alpha-hydroxylase (CYP27B1), and circulating biomarkers were measured in fasting blood samples from volunteers (n = 748) starting IMT. Volunteers were block randomized by race and sex to receive Ca (2000 mg) and vitamin D (1000 IU) or placebo daily throughout Army or Air Force IMT (7 to 9 weeks). Total Ca and vitamin D intakes were calculated as the sum of supplemental intake based on intervention compliance and dietary intake. Relationships between SNPs, Ca, and vitamin D intake tertile and change in biomarkers were evaluated in trial completers (n = 391). At baseline, the minor allele of a DBP SNP (rs7041) was positively associated with both 25OHD (B = 4.46, p = 1.97E-10) and 1,25(OH)2 D3 (B = 9.63, p < 0.001). Combined genetic risk score (GRS) for this SNP and a second SNP in the VDR gene (rs1544410) was inversely associated with baseline 25OHD (r = -0.28, p < 0.001) and response to Ca and vitamin D intake differed by GRS (p < 0.05). In addition, presence of the minor allele of a second VDR SNP (rs2228570) was associated with lower P1NP (B = -4.83, p = 0.04) and osteocalcin (B = -0.59, p = 0.03). These data suggest that VDR and DBP SNPs are associated with 25OHD status and bone turnover and those with the highest GRS require the greatest vitamin D intake to improve 25OHD during IMT. © 2016 American Society for Bone and Mineral Research.