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Association of Polygenic Variants Involved in Immunity and Inflammation with Duodenal Ulcer Risk and Their Interaction with Irregular Eating Habits

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 exa...

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Autores principales: Park, Sunmin, Liu, Meiling, Huang, Shaokai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863374/
https://www.ncbi.nlm.nih.gov/pubmed/36678166
http://dx.doi.org/10.3390/nu15020296
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author Park, Sunmin
Liu, Meiling
Huang, Shaokai
author_facet Park, Sunmin
Liu, Meiling
Huang, Shaokai
author_sort Park, Sunmin
collection PubMed
description 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.
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spelling pubmed-98633742023-01-22 Association of Polygenic Variants Involved in Immunity and Inflammation with Duodenal Ulcer Risk and Their Interaction with Irregular Eating Habits Park, Sunmin Liu, Meiling Huang, Shaokai Nutrients Article 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. MDPI 2023-01-06 /pmc/articles/PMC9863374/ /pubmed/36678166 http://dx.doi.org/10.3390/nu15020296 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Park, Sunmin
Liu, Meiling
Huang, Shaokai
Association of Polygenic Variants Involved in Immunity and Inflammation with Duodenal Ulcer Risk and Their Interaction with Irregular Eating Habits
title Association of Polygenic Variants Involved in Immunity and Inflammation with Duodenal Ulcer Risk and Their Interaction with Irregular Eating Habits
title_full Association of Polygenic Variants Involved in Immunity and Inflammation with Duodenal Ulcer Risk and Their Interaction with Irregular Eating Habits
title_fullStr Association of Polygenic Variants Involved in Immunity and Inflammation with Duodenal Ulcer Risk and Their Interaction with Irregular Eating Habits
title_full_unstemmed Association of Polygenic Variants Involved in Immunity and Inflammation with Duodenal Ulcer Risk and Their Interaction with Irregular Eating Habits
title_short Association of Polygenic Variants Involved in Immunity and Inflammation with Duodenal Ulcer Risk and Their Interaction with Irregular Eating Habits
title_sort association of polygenic variants involved in immunity and inflammation with duodenal ulcer risk and their interaction with irregular eating habits
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863374/
https://www.ncbi.nlm.nih.gov/pubmed/36678166
http://dx.doi.org/10.3390/nu15020296
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