Abstract
Genetic and environmental factors are associated with developing and progressing duodenal ulcer (DU) risk. However, the exact nature of the disease pathophysiology and the single nucleotide polymorphism (SNP)—lifestyle interaction has yet to be determined. The purpose of the present study was to examine the SNPs linked to DU risk and their interaction with lifestyles and diets in a large hospital-based cohort of Asians. Based on an earlier diagnosis, the participants were divided into the DU (case; n = 1088) and non-DU (control, n = 56,713) groups. The SNP associated with DU risk were obtained from a genome-wide association study (GWAS), and those promoted genetic impact with SNP–SNP interactions were identified with generalized multifactor dimensionality reduction analysis. The interaction between polygenic risk score (PRS) calculated from the selected genetic variants and nutrient were examined. They were related to actin modification, immune response, and cell migration by modulating leucine-rich repeats (LRR) domain binding, Shaffer interferon regulatory factor 4 (IRF4) targets in myeloma vs. mature B lymphocyte, and Reactome runt-related transcription factor 3 (RUNX3). Among the selected SNPs, rs11230563 (R225W) showed missense mutation and low binding affinity with different food components in the autodock analysis. Glycyrrhizin, physalin B, janthitrem F, and casuarinin lowered it in only wild CD6 protein but not in mutated CD6. Plastoquinone 8, solamargine, saponin D, and matesaponin 2 decreased energy binding affinity in mutated CD6 proteins. The PRS of the 5-SNP and 6-SNP models exhibited a positive association with DU risk (OR = 3.14). The PRS of the 5-SNP PRS model interacted with irregular eating habits and smoking status. In participants with irregular eating habits or smokers, DU incidence was much higher in the participants with high PRS than in those with low PRS. In conclusion, the genetic impact of DU risk was mainly in regulating immunity, inflammation, and actin modification. Adults who are genetically susceptible to DU need to eat regularly and to be non-smokers. The results could be applied to personalize nutrition.
Funder
National Research Foundation of Korea
Subject
Food Science,Nutrition and Dietetics
Reference49 articles.
1. Xie, X., Ren, K., Zhou, Z., Dang, C., and Zhang, H. (2022). The global, regional and national burden of peptic ulcer disease from 1990 to 2019: A population-based study. BMC Gastroenterol., 22.
2. Malik, T.F., Gnanapandithan, K., and Singh, K. (2022). Peptic Ulcer Disease, StatPearls.
3. Peptic Ulcer Disease Associated with Helicobacter pylori Infection;Yeo;Korean J. Gastroenterol.,2016
4. Vona, R., Pallotta, L., Cappelletti, M., Severi, C., and Matarrese, P. (2021). The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders. Antioxidants, 10.
5. Helicobacter pylori-Mediated Oxidative Stress and Gastric Diseases: A Review;Han;Front. Microbiol.,2022
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献