Genetic Polymorphisms in Fatty Acid Metabolism Modify the Association Between Dietary n3

Ananthakrishnan, Ashwin N.; Khalili, Hamed; Song, Mingyang; Higuchi, Leslie M.; Lochhead, Paul; Richter, James M.; Chan, Andrew T.

doi:10.1097/mib.0000000000001236

Cited by 32 publications

(29 citation statements)

References 56 publications

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“…The cluster is built about a 283 kb region on chromosome 11 that contains the DAGLA, MYRF, TMEM258, RP11-467L20, FADS1, FADS2, FADS3 , and BEST1 genes (Fig 2b; S3 Table). Consistent with this observation, genetic variations in the FADS1 – FADS3 region have previously been associated with alterations in the synthesis of PUFAs 32 , inflammatory bowel diseases 33 , cholesterol levels and BMI 34 , coronary artery disease and type 2 diabetes 35 , and colorectal cancer 36 .…”

Section: Resultssupporting

confidence: 61%

Chromatin interactions and expression quantitative trait loci reveal genetic drivers of multimorbidities

Fadason

Schierding

Lumley

et al. 2018

Preprint

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Clinical studies of non-communicable diseases identify multimorbidities that reflect our relatively limited fixed metabolic capacity. Despite the fact that we have ∼24000 genes, we do not understand the genetic pathways that contribute to the development of multimorbid non-communicable disease. We created a “multimorbidity atlas” of traits based on pleiotropy of spatially regulated genes using convex biclustering. Using chromatin interaction and expression Quantitative Trait Loci (eQTL) data, we analysed 20,782 variants (p < 5 × 10−6) associated with 1,351 phenotypes, to identify 16,248 putative eQTL-eGene pairs that are involved in 76,013 short- and long-range regulatory interactions (FDR < 0.05) in different human tissues. Convex biclustering of eGenes that are shared between phenotypes identified complex inter-relationships between nominally different phenotype associated SNPs. Notably, the loci at the centre of these inter-relationships were subject to complex tissue and disease specific regulatory effects. The largest cluster, 40 phenotypes that are related to fat and lipid metabolism, inflammatory disorders, and cancers, is centred on the FADS1-FADS3 locus (chromosome 11). Our novel approach enables the simultaneous elucidation of variant interactions with genes that are drivers of multimorbidity and those that contribute to unique phenotype associated characteristics.

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Section: Resultssupporting

confidence: 61%

Chromatin interactions and expression quantitative trait loci reveal genetic drivers of multimorbidities

Fadason

Schierding

Lumley

et al. 2018

Preprint

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“…In contrast, the diet–gene interaction model has also been a controversial topic. A recent nested case–control study reported that no association was found between the ratio of n-6 to n-3 PUFAs and the risk of Crohn's disease under consideration of SNPs at CYP4F3 and FADS2 loci [ 36 ].…”

Section: Epidemiology Of Diet and Crohn's Diseasementioning

confidence: 99%

Lipid and Bile Acid Dysmetabolism in Crohn’s Disease

Uchiyama

Kishi

Komatsu

et al. 2018

Journal of Immunology Research

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Crohn's disease is one of the systemic autoimmune diseases. It commonly affects the small intestine and colon but may involve any portion of the gastrointestinal tract from the mouth to the anus. The most affected area by Crohn's disease is the distal part of the small intestine, in which the bile acid molecules are most efficiently reabsorbed. Bile acids form mixed micelles together with fatty acids, which function as a transport vehicle to deliver fatty acids to the apical membrane of enterocytes for absorption. Therefore, if the terminal ileum is impaired, bile acid malabsorption may occur, which may cause congenital diarrhoea in Crohn's disease. Similarly, the impairment of the terminal ileum also induces fatty acid malabsorption, which may influence the role of fatty acids in Crohn's disease. In contrast, a recent study reported that multidrug resistance protein 1 (MDR1) regulated effector T-cell function in the ileum from bile acid-driven oxidative stress and MDR1 loss of function in a subset of patients with Crohn's disease. However, the role of consumption of fatty acids in Crohn's disease remains to be fully elucidated. This review is aimed at providing an overview of some recent developments in research of Crohn's disease from comprehensive perspective with a focus on the connection between disease location and behaviour, lipid diets, and bile acid malabsorption.

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“…A case-control study has suggested that the association between dietary n3: n6 PUFA intake and risk of UC may be modified variants at CYP4F3. High n3: n6 PUFA intake was associated with reduced risk of UC in individuals with GG/AG genotype at a single nucleotide polymorphism in CYP4F3 [114] . Barnes EL et al [115] reported that increased intake of multiple fatty acids was associated with increasing odds of relapse and specific fatty acids, i.e., myristic acid (commonly found in palm oil, coconut oil, and dairy fats) that may associate with an increasing risk of flare.…”

Section: (4) Sarcopeniamentioning

confidence: 94%

Significance of nutritional treatment for patients with inflammatory bowel disease in the era of biologics

Yokoyama¹,

Iida²,

Nakase³

2019

OJGH

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Review Article OJGH (2019) 2:20 Significance of nutritional treatment for patients with inflammatory bowel disease in the era of biologics Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease (CD), is a chronic gastrointestinal tract inflammatory disorder. Although its etiology remains unknown, it has been reported that nutrition is involved in the onset of IBD. Patients with IBD often experience malnutrition due to malabsorption and increased energy requirements. Malnutrition is a serious issue for patients with IBD, especially in young people. Growth retardation characterized by delayed skeletal maturation and onset of puberty is a representative complication. In addition, immunosuppression, osteoporosis, and sarcopenia are important issues. Functional foods and diets have been known to alleviate gastrointestinal inflammation by modulating inflammatory cytokines. Furthermore, appropriate nutritional treatment has been reported to be effective on the induction and maintenance of remission in patients with IBD, especially with CD. Conversely, there are negative reports regarding the efficacy of nutritional therapy in patients with IBD. Recently, various new therapeutic agents such as biologics have emerged as key drugs in IBD treatment. In this new era, the efficacy of nutritional treatment, including combination therapy with biologics, should be reconsidered to improve the quality of life in patients with IBD. In this review, the nutritional treatment for patients with IBD is reviewed, and the latest evidence is provided.

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Genetic Polymorphisms in Fatty Acid Metabolism Modify the Association Between Dietary n3

Cited by 32 publications

References 56 publications

Chromatin interactions and expression quantitative trait loci reveal genetic drivers of multimorbidities

Chromatin interactions and expression quantitative trait loci reveal genetic drivers of multimorbidities

Lipid and Bile Acid Dysmetabolism in Crohn’s Disease

Significance of nutritional treatment for patients with inflammatory bowel disease in the era of biologics

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