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The impact of diet patterns and PUFA-related polymorphisms on ulcerative colitis in Hispanics

饮食模式和 PUFA 相关多态性对西班牙裔溃疡性结肠炎的影响

基本信息

批准号：
10528451
负责人：
Oriana Mazorra Damas
金额：
$ 18.49万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-14 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10528451
关键词：
Adoption Adult Affect Age of Onset Biochemical Biological Chronic Clinic Clinical Colitis Collection Colonic inflammation Crohn&apos s disease Data Defecation Development Diet Dietary History Dietary Intervention Dietary Practices Dietary Questionnaires Dietary intake Disease Disease remission Enzymes European Fatty Acids Feces Food Frequencies Future Generations Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Genetic Risk Genetic Variation Hemorrhage Heterogeneity Hispanic Hispanic Americans Hispanic Populations Hospitalization Immune Incidence Individual Inflammation Inflammatory Inflammatory Bowel Diseases Intake Intervention Studies Leukocyte L1 Antigen Complex Measures Mediating Mentors Metabolic Modeling N-3 polyunsaturated fatty acid Omega-3 Fatty Acids Omega-6 Fatty Acids Participant Pathway interactions Patients Pattern Pharmaceutical Preparations Phenotype Polyunsaturated Fatty Acids Prevalence Prospective Studies Questionnaires Recommendation Rectum Recurrent disease Regression Analysis Relapse Reporting Reproducibility Research Research Personnel Resources Risk Role Severities Severity of illness Surveys Testing Ulcerative Colitis Universities Variant Work bilingualism career cohort design dietary disease phenotype fatty acid biosynthesis fatty acid metabolism follow-up gene environment interaction genetic variant genome sequencing indexing microbiome research novel population based programs rectal relapse patients risk variant tool western diet whole genome

项目摘要

Summary Ulcerative colitis (UC) is a devastating immune-mediated disease that is on the rise globally. In our prior study, we found that Hispanics have less severe disease than non-Hispanics, but yet within one US-born generation develop a disease course that is similar. Differences in adoption of a Western diet between US- born and foreign-born Hispanics could explain differences in UC severity observed. A Western diet, high in n-6 to n-3 polyunsaturated fatty acids (PUFA), is up to 10-20 times the recommended intake and is considered pro- inflammatory. However, heterogeneity of results in dietary intervention studies suggests that underlying genetic variation in PUFA metabolism may modify diet effects. Our preliminary data indicates that Hispanics with UC have polymorphisms in PUFA not present in Hispanic controls. In UC, disease activity measured by rectal bleeding, number of bowel movements, and urgency correlates with endoscopic inflammation. I hypothesize that Hispanics with UC whose diet follows a higher Western dietary pattern, defined by a reproducible dietary pattern score, have more active disease, than those whose diet scores are lower. Further, I propose that carriage of PUFA variants augments the effect of a Western diet on relapse leading to a disproportionate pro- inflammatory effect of the diet. In this study, I examine the influence of a Western dietary pattern on remission and relapse of UC among Hispanics (Aim 1). We will test whether PUFA variants influence relapse and enhance the effect of a Western diet on UC relapse (Aim 2). A total of 320 self- identified, Hispanic participants with UC are followed at our GI clinics and we will include these for our diet portion in Aim 1. We will include a total of 691 Hispanics with UC and 900 Hispanic controls for our Aim 2 genetics portion. We have detailed demographic and clinical information on these patients, as well as whole genome sequencing of PUFA variants. Participants will be asked to complete a validated food-frequency dietary questionnaire, at baseline and at 1-year follow up. Disease activity using the validated simple clinical colitis activity index will be assessed at baseline and at 1 year follow up in combination with fecal calprotectin. We will calculate scores for a Western dietary pattern and determine the influence of diet on relapse using multivariable regression analysis. In Aim 2, we will examine the effect of PUFA variants on relapse and also determine gene-environment interactions influencing disease activity between PUFA variants and Western diet. Results gathered from this study will be a step towards personalizing IBD treatment by targeting specific dietary patterns in Hispanics with highest metabolic genetic risk.

总结