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Genetic Polymorphisms in Fatty Acid Metabolism Modify the Association Between Dietary n3: n6 Intake and Risk of Ulcerative Colitis: A Prospective Cohort Study.

ABSTRACT: INTRODUCTION:High intake of dietary n-3 polyunsaturated fatty acids (PUFA) is associated with a decreased risk of ulcerative colitis (UC) and Crohn's disease (CD). However, results have been heterogeneous suggesting that genetic variations in PUFA metabolism may modify this risk. METHODS:We conducted a case-control study nested within 2 prospective cohorts, the Nurses' Health Study (NHS) and NHS II. Among women providing blood (n = 62,437) or buccal cells (n = 59,543) for genotyping, we confirmed new diagnoses of CD or UC. Dietary intake was assessed 4 years before diagnosis. Confirmed cases were matched 1:2 to controls. Subjects were genotyped for single nucleotide polymorphisms at CYP4F3, FADS1, and FADS2 loci. Conditional logistic regression models examined the interaction between genotype, n3:n6 PUFA intake and risk of CD and UC. RESULTS:Our study included 101 CD and 139 UC patients matched to 495 controls. On multivariable analysis, high intake of n3:n6 PUFA (above median) demonstrated a trend toward reduced risk of UC (Odds ratio [OR] 0.71, 95% confidence interval [CI], 0.47-1.09, P = 0.11). High n3:n6 PUFA intake was associated with a reduced risk of UC in individuals with the GG/AG genotype at a single nucleotide polymorphism in CYP4F3 (OR 0.57, 95% CI, 0.32-0.99) but not those with the AA genotype (OR 0.95, 95% CI, 0.47-1.93) (P-interaction = 0.049). No gene-diet interactions were noted for CD. CONCLUSIONS:The association between dietary n3:n6 PUFA intake and risk of UC may be modified variants at CYP4F3. Further gene-environment studies of the association between diet and IBD risk are warranted.

SUBMITTER: Ananthakrishnan AN

PROVIDER: S-EPMC5675119 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Genetic Polymorphisms in Fatty Acid Metabolism Modify the Association Between Dietary n3: n6 Intake and Risk of Ulcerative Colitis: A Prospective Cohort Study.

Ananthakrishnan Ashwin N AN Khalili Hamed H Song Mingyang M Higuchi Leslie M LM Lochhead Paul P Richter James M JM Chan Andrew T AT

Inflammatory bowel diseases 20171101 11

<h4>Introduction</h4>High intake of dietary n-3 polyunsaturated fatty acids (PUFA) is associated with a decreased risk of ulcerative colitis (UC) and Crohn's disease (CD). However, results have been heterogeneous suggesting that genetic variations in PUFA metabolism may modify this risk.<h4>Methods</h4>We conducted a case-control study nested within 2 prospective cohorts, the Nurses' Health Study (NHS) and NHS II. Among women providing blood (n = 62,437) or buccal cells (n = 59,543) for genotypi ...[more]

PMID: 28991856

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Project description:BackgroundPolyunsaturated fatty acids (PUFAs) are associated with a lower risk of multiple diseases. Fatty acid desaturase 1 gene (FADS1) polymorphisms and dietary PUFA intake are both established determinants of circulating PUFA proportions.ObjectiveWe explored the joint effects of FADS1 polymorphisms and dietary PUFA intake on circulating PUFA proportions.DesignWe studied 2288 participants from a nested case-control study of coronary artery disease among participants who provided blood samples in the Nurses' Health Study and the Health Professionals Follow-Up Study. Dietary PUFA intake was obtained from semiquantitative food-frequency questionnaires. FADS1 rs174546 was genotyped by using the Affymetrix 6.0 platform, and circulating PUFA proportions were measured with gas-liquid chromatography. Linear regression models were used to examine the associations between rs174546 and circulating proportions of each fatty acid. Gene-diet interactions were tested by including a cross-product term of dietary intake of each PUFA by rs174546 genotype in the linear regression models.ResultsAfter adjustment for sex and ancestry, each copy of the C allele of rs174546 was associated with higher circulating proportions of arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and lower proportions of linoleic acid and α-linolenic acid. The magnitude of positive association between higher consumption of dietary EPA or DHA and circulating proportions of EPA increased with each copy of the rs174546_T allele (P-interaction = 0.01 and 0.007, respectively). Each 1-SD increment in EPA intake was associated with an average 3.7% increase in circulating EPA proportions among participants with the rs174546_CC genotype and an average 7.8% increase among participants with the TT genotype.ConclusionsCarriers of the T allele at FADS1 rs174546 may need higher doses of dietary EPA and DHA to achieve the same circulating proportions of EPA as carriers of the C allele. The implications of these findings on disease risk and dietary guidelines require further study.

Project description:A growing number of healthy dietary ingredients in fruits and vegetables have been shown to exhibit diverse biological activities. Phloretin, a dihydrochalcone flavonoid that is abundant in apples and pears, has anti-inflammatory effects on ulcerative colitis (UC) mice. The gut microbiota and metabolism are closely related to each other due to the existence of the food-gut axis in the human colon. To investigate the interplay of faecal metabolites and the microbiota in UC mice after phloretin treatment, phloretin (60 mg/kg) was administered by gavage to ameliorate dextran sulfate sodium (DSS)-induced UC in mice. Gut microbes and faecal metabolite profiles were detected by high-throughput sequencing and liquid chromatography mass spectrometry (LC-MS) analysis, respectively. The correlations between gut microbes and their metabolites were evaluated by Spearman correlation coefficients. The results indicated that phloretin reshaped the disturbed faecal metabolite profile in UC mice and improved the metabolic pathways by balancing the composition of faecal metabolites such as norepinephrine, mesalazine, tyrosine, 5-acetyl-2,4-dimethyloxazole, and 6-acetyl-2,3-dihydro-2-(hydroxymethyl)-4(1H)-pyridinone. Correlation analysis identified the relations between the gut microbes and their metabolites. Proteus was negatively related to many faecal metabolites, such as norepinephrine, L-tyrosine, laccarin, dopamine glucuronide, and 5-acetyl-2,4-dimethyloxazole. The abundance of unidentified Bacteriodales_S24-7_group was positively related to ecgonine, 15-KETE and 6-acetyl-2,3-dihydro-2-(hydroxymethyl)-4(1H)-pyridinone. The abundance of Christensenellaceae_R-7_group was negatively related to the levels of 15-KETE and netilmicin. Stenotrophomonas and 15-KETE were negatively related, while Intestinimonas and alanyl-serine were positively related. In conclusion, phloretin treatment had positive impacts on faecal metabolites in UC mice, and the changes in faecal metabolites were closely related to the gut microbiota.

Dataset Information

Genetic Polymorphisms in Fatty Acid Metabolism Modify the Association Between Dietary n3: n6 Intake and Risk of Ulcerative Colitis: A Prospective Cohort Study.

Publications

Genetic Polymorphisms in Fatty Acid Metabolism Modify the Association Between Dietary n3: n6 Intake and Risk of Ulcerative Colitis: A Prospective Cohort Study.

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