Key Genotypes and the Response to Nutrient Supplementation in Crohn’s Disease

Abstract

Background New Zealand has high rates of Crohn’s disease (CD) at 26/10. Having gene variants associated with low levels of betacarotene, vitamin D and Omega-3 polyunsaturated fatty acids can impede the immune response. Not known is the prevalence of these variants in a New Zealand CD population. Methods Project One To identify in New Zealand adults with CD (n=443) and healthy (n=649) the prevalence of gene variants associated with: low betacarotene absorption (BCMO1); low vitamin D concentrations (GC, NADSYN1, CYP24A1, CYP2R1); omega-three and-six fatty acid uptake (FADS1, FADS2); cholesterol (PPARA); cardiovascular risk and CD activity (PPARG); colorectal adenoma (XRCC1), and inflammation (SCD). Project Two To investigate, through a double blinded, randomized, placebo, crossover, 12 week trial, the response of 30 healthy adults to a commercial nutrient supplement (containing antioxidants, vitamin D (25(OH)D3) and long chain Omega-3 fatty acids, in contrast to a medium-chain triglyceride oil (MCT) placebo, by measuring changes in inflammatory markers, biomarkers (blood lipids, serum concentrations of fatty acids, vitamin D and carotenoids, stool DNA (for microbiota), gene expression shifts in inflammatory genes, and environmental data (stool, quality of life and nutrition measures). Project Three To investigate the response of 30 adults with CD to the same commercial nutrient supplement using similar methodology. Results Data analysis revealed gene variants from three SNPs: rs12934922, (BCM01); rs1074165, (CYP2R1) and rs174583 (FADS2) associated with low betacarotene absorption, low vitamin D concentration and negative fatty acid interactions respectively had frequencies of 18, 39 and 16% respectively in healthy and CD groups. In the nutrient supplement trials, healthy and CD groups showed significantly increased levels of EPA, (p=6.68E-14, p=2.20E-05) DHA (p=3.09E-09, p=9.10E-04), DPA (p=9.65E-09, p=0.01), HDL (p=0.011, p=0.001), and food variety scores (p=0.001, p=0.0168) and a significant decrease in the Chol/HDL ratio (p=0.006, p=0.026) respectively. In healthy adults the MCT placebo significantly reduced vitamin D levels (p=0.0001). The CD group showed significant decreases in DNA damage (p=0.0003). Conclusion Those carrying key gene variants are susceptible to low levels of ant-inflammatory nutrients. The supplement benefits the nutrient profiles in both groups within a short time frame and reduced DNA damage in the CD group.