{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:59:50Z","timestamp":1789682390917,"version":"4.0.1"},"reference-count":49,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A2C1007203"],"award-info":[{"award-number":["2019R1A2C1007203"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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)\u2014lifestyle 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\u2013SNP 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.<\/jats:p>","DOI":"10.3390\/nu15020296","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T04:42:17Z","timestamp":1673239337000},"page":"296","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Association of Polygenic Variants Involved in Immunity and Inflammation with Duodenal Ulcer Risk and Their Interaction with Irregular Eating Habits"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6092-8340","authenticated-orcid":false,"given":"Sunmin","family":"Park","sequence":"first","affiliation":[{"name":"Department of Food and Nutrition, Obesity\/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea"},{"name":"Department of Bioconvergence, Hoseo University, Asan 31499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Obesity\/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaokai","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Bioconvergence, Hoseo University, Asan 31499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"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.","DOI":"10.1186\/s12876-022-02130-2"},{"key":"ref_2","unstructured":"Malik, T.F., Gnanapandithan, K., and Singh, K. (2022). Peptic Ulcer Disease, StatPearls."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"289","DOI":"10.4166\/kjg.2016.67.6.289","article-title":"Peptic Ulcer Disease Associated with Helicobacter pylori Infection","volume":"67","author":"Yeo","year":"2016","journal-title":"Korean J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"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.","DOI":"10.3390\/antiox10020201"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"811258","DOI":"10.3389\/fmicb.2022.811258","article-title":"Helicobacter pylori-Mediated Oxidative Stress and Gastric Diseases: A Review","volume":"13","author":"Han","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"684162","DOI":"10.3389\/fphar.2021.684162","article-title":"Pharmacogenomics of NSAID-Induced Upper Gastrointestinal Toxicity","volume":"12","author":"McEvoy","year":"2021","journal-title":"Front. Pharm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.humimm.2007.10.006","article-title":"Association of Toll-like receptor-4 (Asp299Gly and Thr399Ileu) gene polymorphisms with gastritis and precancerous lesions","volume":"68","author":"Achyut","year":"2007","journal-title":"Hum. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e7612","DOI":"10.1097\/MD.0000000000007612","article-title":"The impact of host\u2019s genetic susceptibility on Helicobacter pylori infection in children","volume":"96","author":"Moldovan","year":"2017","journal-title":"Medicine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"371","DOI":"10.15403\/jgld.2014.1121.274.cat","article-title":"The CAT-262 C>T, MnSOD Ala16Val, GPX1 Pro198Leu Polymorphisms Related to Oxidative Stress and the Presence of Gastric Lesions","volume":"27","author":"Negovan","year":"2018","journal-title":"J. Gastrointestin. Liver. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1038\/s41467-021-21280-7","article-title":"GWAS of peptic ulcer disease implicates Helicobacter pylori infection, other gastrointestinal disorders and depression","volume":"12","author":"Wu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/ng.1109","article-title":"A genome-wide association study identifies two susceptibility loci for duodenal ulcer in the Japanese population","volume":"44","author":"Tanikawa","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1080\/00365520701742930","article-title":"Gastric carcinogenesis: Possible role of polymorphisms of GSTM1, GSTT1, and GSTP1 genes","volume":"43","author":"Tripathi","year":"2008","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1002\/humu.22040","article-title":"Association of glycosylated hemoglobin with the gene encoding CDKAL1 in the Korean Association Resource (KARE) study","volume":"33","author":"Ryu","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.nut.2016.07.001","article-title":"Interaction of BDNF rs6265 variants and energy and protein intake in the risk for glucose intolerance and type 2 diabetes in middle-aged adults","volume":"33","author":"Daily","year":"2017","journal-title":"Nutrition"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12986-016-0096-8","article-title":"Interactions with the MC4R rs17782313 variant, mental stress, and energy intake and the risk of obesity in Genome Epidemiology Study","volume":"13","author":"Park","year":"2016","journal-title":"Nutr. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wu, X., and Park, S. (2021). An Inverse Relation between Hyperglycemia and Skeletal Muscle Mass Predicted by Using a Machine Learning Approach in Middle-Aged and Older Adults in Large Cohorts. J. Clin. Med., 10.","DOI":"10.3390\/jcm10102133"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Park, S., Kim, C., and Wu, X. (2022). Development and Validation of an Insulin Resistance Predicting Model Using a Machine-Learning Approach in a Population-Based Cohort in Korea. Diagnostics, 12.","DOI":"10.3390\/diagnostics12010212"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.3346\/jkms.2015.30.9.1279","article-title":"Self-rated Subjective Health Status Is Strongly Associated with Sociodemographic Factors, Lifestyle, Nutrient Intakes, and Biochemical Indices, but Not Smoking Status: KNHANES 2007\u20132012","volume":"30","author":"Park","year":"2015","journal-title":"J. Korean Med. Sci."},{"key":"ref_19","first-page":"47","article-title":"TRPV1 Gene Polymorphisms Are Associated with Type 2 Diabetes by Their Interaction with Fat Consumption in the Korean Genome Epidemiology Study","volume":"9","author":"Park","year":"2016","journal-title":"J. Nutrigenet. Nutr."},{"key":"ref_20","unstructured":"Steel, R.G., Torrie, J.H., and Dickey, D.A. (1997). Principles and Procedures of Statistics: A Biological Approach, McGraw-Hill College."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kim, J.O., and Mueller, C.W. (1978). Factor Analysis. Statistical Methods and Practical Issues, Sage Publications.","DOI":"10.4135\/9781412984256"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.3945\/ajcn.112.056333","article-title":"Adapted dietary inflammatory index and its association with a summary score for low-grade inflammation and markers of glucose metabolism: The Cohort study on Diabetes and Atherosclerosis Maastricht (CODAM) and the Hoorn study","volume":"98","author":"Theofylaktopoulou","year":"2013","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1017\/S0007114515005152","article-title":"Relationship of sodium intake with obesity among Korean children and adolescents: Korea National Health and Nutrition Examination Survey","volume":"115","author":"Lee","year":"2016","journal-title":"Br. J. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e20","DOI":"10.1093\/ije\/dyv316","article-title":"Cohort Profile: The Korean Genome and Epidemiology Study (KoGES) Consortium","volume":"46","author":"Kim","year":"2017","journal-title":"Int. J. Epidemiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/bioinformatics\/bti741","article-title":"A genotype calling algorithm for affymetrix SNP arrays","volume":"22","author":"Rabbee","year":"2006","journal-title":"Bioinformatics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.mgene.2015.05.001","article-title":"Gene-gene and gene-environment interactions in the etiology of type 2 diabetes mellitus in the population of Hyderabad, India","volume":"5","author":"Reddy","year":"2015","journal-title":"Meta Gene"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1089\/jmf.2021.K.0144","article-title":"Bioactive Components of Houttuynia cordata Thunb and Their Potential Mechanisms against COVID-19 Using Network Pharmacology and Molecular Docking Approaches","volume":"25","author":"Yuan","year":"2022","journal-title":"J. Med. Food"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yang, Y., Shi, C.-Y., Xie, J., Dai, J.-H., He, S.-L., and Tian, Y. (2020). Identification of potential dipeptidyl peptidase (DPP)-IV inhibitors among Moringa oleifera phytochemicals by virtual screening, molecular docking analysis, ADME\/T-based prediction, and in vitro analyses. Molecules, 25.","DOI":"10.3390\/molecules25010189"},{"key":"ref_29","unstructured":"(2016). SAS\/STAT\u00ae 14.2 User\u2019s Guide, SAS Inc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.4162\/nrp.2022.16.S1.S1","article-title":"Dietary Reference Intakes for Koreans with special consideration to older adults","volume":"16","author":"Kim","year":"2022","journal-title":"Nutr. Res. Pract."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.2174\/1381612824666180510092303","article-title":"Lifestyle and Peptic Ulcer Disease","volume":"24","author":"Yegen","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.micres.2018.09.011","article-title":"Helicobacter pylori evasion strategies of the host innate and adaptive immune responses to survive and develop gastrointestinal diseases","volume":"218","author":"Karkhah","year":"2019","journal-title":"Microbiol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"fty078","DOI":"10.1093\/femspd\/fty078","article-title":"Expression levels of A disintegrin and metalloproteases (ADAMs), and Th17-related cytokines and their association with Helicobacter pylori infection in patients with gastroduodenal diseases","volume":"76","author":"Khatoon","year":"2018","journal-title":"Pathog. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhang, B.B., Liu, X.Z., Sun, J., Yin, Y.W., and Sun, Q.Q. (2013). Association between TNF \u03b1 gene polymorphisms and the risk of duodenal ulcer: A meta-analysis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057167"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1002\/humu.20299","article-title":"Interaction between IL1B gene promoter polymorphisms in determining susceptibility to Helicobacter pylori associated duodenal ulcer","volume":"27","author":"Chakravorty","year":"2006","journal-title":"Hum. Mutat."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.cca.2007.12.008","article-title":"IL-4 -588C>T polymorphism and IL-4 receptor alpha [Ex5+14A>G.; Ex11+828A>G] haplotype concur in selecting H. pylori cagA subtype infections","volume":"389","author":"Zambon","year":"2008","journal-title":"Clin. Chim. Acta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"362","DOI":"10.5009\/gnl15129","article-title":"The IL-1B Genetic Polymorphism Is Associated with Aspirin-Induced PepticUlcers in a Korean Ethnic Group","volume":"10","author":"Cho","year":"2016","journal-title":"Gut Liver"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1111\/j.1440-1746.2008.05563.x","article-title":"Inflammatory cytokine gene polymorphisms and gastric cancer","volume":"23","author":"Lee","year":"2008","journal-title":"J. Gastrogenterol. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.2217\/fon-2016-0233","article-title":"Interaction between Helicobacter pylori and host genetic variants in gastric carcinogenesis","volume":"12","author":"Jia","year":"2016","journal-title":"Future Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gareb, B., Otten, A.T., Frijlink, H.W., Dijkstra, G., and Kosterink, J.G.W. (2020). Review: Local Tumor Necrosis Factor-\u03b1 Inhibition in Inflammatory Bowel Disease. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12060539"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1212\/WNL.60.1.22","article-title":"Mutation of a putative protein degradation gene LITAF\/SIMPLE in Charcot-Marie-Tooth disease 1C","volume":"60","author":"Street","year":"2003","journal-title":"Neurology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1002\/ijc.29500","article-title":"Association of PSCA rs2294008 gene variants with poor prognosis and increased susceptibility to gastric cancer and decreased risk of duodenal ulcer disease","volume":"137","author":"Bujanda","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1093\/carcin\/bgy151","article-title":"Variants in the PSCA gene associated with risk of cancer and nonneoplastic diseases: Systematic research synopsis, meta-analysis and epidemiological evidence","volume":"40","author":"Cui","year":"2019","journal-title":"Carcinogenesis"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liao, J., Wen, S., Cao, L., Zhou, Y., and Feng, Z. (2015). Effect of eradication of Helicobacter pylori on expression levels of FHIT, IL-8, and P73 in gastric mucosa of first-degree relatives of gastric cancer patients. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124576"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/s41467-021-20993-z","article-title":"Calcium channel ITPR2 and mitochondria\u2013ER contacts promote cellular senescence and aging","volume":"12","author":"Ziegler","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e14384","DOI":"10.14814\/phy2.14384","article-title":"Multiple calcium sources are required for intracellular calcium mobilization during gastric organoid epithelial repair","volume":"8","author":"Engevik","year":"2020","journal-title":"Physiol. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1021\/acs.jcim.7b00564","article-title":"Relative Binding Free Energy Calculations in Drug Discovery: Recent Advances and Practical Considerations","volume":"57","author":"Cournia","year":"2017","journal-title":"J. Chem. Inform. Model."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"619","DOI":"10.2174\/1389450116666150825120536","article-title":"CD6 as a Cell Surface Receptor and As a Target for Regulating Immune Responses","volume":"17","author":"Brown","year":"2016","journal-title":"Curr. Drug Targets"},{"key":"ref_49","first-page":"e22001","article-title":"Risk Factors for Recurrence of Peptic Ulcer Disease: A Retrospective Study in Tertiary Care Referral Center","volume":"14","author":"Alsinnari","year":"2022","journal-title":"Cureus"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/2\/296\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:01:53Z","timestamp":1760119313000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/2\/296"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,6]]},"references-count":49,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["nu15020296"],"URL":"https:\/\/doi.org\/10.3390\/nu15020296","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,6]]}}}