Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea.
Department of Bioconvergence, Hoseo University, Asan 31499, Republic of Korea.
Nutrients. 2023 Jan 6;15(2):296. doi: 10.3390/nu15020296.
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.
遗传和环境因素与十二指肠溃疡 (DU) 风险的发展和进展有关。然而，疾病病理生理学的确切性质以及单核苷酸多态性 (SNP)-生活方式的相互作用尚未确定。本研究的目的是在一个大型基于医院的亚洲人群中检查与 DU 风险相关的 SNPs 及其与生活方式和饮食的相互作用。根据早期诊断，将参与者分为 DU（病例；n = 1088）和非-DU（对照组，n = 56713）组。从全基因组关联研究 (GWAS) 中获得与 DU 风险相关的 SNP，并用广义多因素降维分析识别促进遗传影响的 SNP-SNP 相互作用。检查从选定遗传变异计算得出的多基因风险评分 (PRS) 与营养素之间的相互作用。它们通过调节富含亮氨酸重复 (LRR) 结构域结合、Shaffer 干扰素调节因子 4 (IRF4) 在骨髓瘤与成熟 B 淋巴细胞中的靶标以及 Reactome runt 相关转录因子 3 (RUNX3)，来调节肌动蛋白修饰、免疫反应和细胞迁移。在所选择的 SNP 中，rs11230563（R225W）在自动对接分析中显示出错义突变和与不同食物成分的低结合亲和力。甘草酸、黄芹素 B、姜黄呋喃 F 和 casuarinin 仅在野生 CD6 蛋白中降低了它，但在突变 CD6 中没有。质体醌 8、番茄碱、皂甙 D 和马替皂甙 2 降低了突变 CD6 蛋白的能量结合亲和力。5-SNP 和 6-SNP 模型的 PRS 与 DU 风险呈正相关（OR = 3.14）。5-SNP PRS 模型的 PRS 与不规律的饮食习惯和吸烟状况相互作用。在不规律的饮食习惯或吸烟者中，高 PRS 参与者的 DU 发生率明显高于低 PRS 参与者。总之，DU 风险的遗传影响主要在于调节免疫、炎症和肌动蛋白修饰。易患 DU 的成年人需要有规律地进食和不吸烟。研究结果可应用于个性化营养。
