幽门螺杆菌相关消化不良患者中 NOD1、白细胞介素-1B 和 cagA 菌株的遗传多态性与低度十二指肠炎性嗜酸性粒细胞增多的关系。

Association between genetic polymorphisms of NOD1, Interleukin-1B, and cagA strain with low-grade duodenal eosinophilia in Helicobacter pylori-related dyspepsia.

机构信息

Laboratorio de Biotecnología Molecular (BIOTECMOL)., Instituto de Biotecnología de Misiones "Dra. Maria Ebbe Reca" (InBioMis). Facultad de Ciencias Exactas Químicas y Naturales. Universidad Nacional de Misiones, Posadas, Argentina.

CONICET, Buenos Aires, Argentina.

出版信息

Helicobacter. 2023 Oct;28(5):e13002. doi: 10.1111/hel.13002. Epub 2023 Jun 23.

DOI:10.1111/hel.13002

PMID:37350445

Abstract

BACKGROUND

Functional dyspepsia (FD) is a multifactorial disorder. Helicobacter pylori (H. pylori)-related dyspepsia (HpD) may be considered a separate entity. Duodenal eosinophilia is a potential pathogenic mechanism in FD. However, the impact of duodenal eosinophilia and host genetic polymorphism of innate and pro-inflammatory cascade, nucleotide-binding oligomerization domain 1 (NOD-1), and interleukin-1 beta (IL-1β) in HpD was not explored.

AIM

To evaluate the association of NOD1-796G>A and IL-1B-511C>T gene variants and low-grade duodenal eosinophilia in HpD.

METHODS

A multicenter cross-sectional study was conducted. A total of 253 patients who met Rome-IV criteria were selected before upper endoscopy and 98 patients were included after unremarkable upper endoscopy and positive H. pylori in gastric biopsies were assessed. Clinical parameters, H. pylori cagA and duodenal histology, were evaluated.

RESULTS

Sixty-four (65%) patients had epigastric pain syndrome (EPS), 24 (25%) postprandial distress syndrome (PDS), and 10 (10%) EPS/PDS overlap. FD subtypes were not associated with NOD1-796G>A and IL-1B-511C>T gene variants. Low-grade duodenal eosinophilia was significantly increased in NOD1-796 GG versus single A-allele, but not in IL-1B-511 single T-allele or CC-allele. This association is dependent of cagA infection, since harboring cagA strain was significantly associated with low-grade duodenal eosinophilia with isolated variants NOD1-796 GG and IL-1B-511 single T-allele, but not without cagA. When we performed combined polymorphism analysis with NOD1-796 GG/IL-1B-511 single T-allele, a synergistic effect on low-grade duodenal eosinophilia was found between these two loci irrespective of cagA strain status in HpD.

CONCLUSION

Our findings suggest that low-grade duodenal eosinophilia is significantly associated with NOD1-796 GG allele specially in cagA strain and with allelic combination NOD1-796 GG/IL-1B-511 single T-allele independent of cagA strain infection in HpD patients.

摘要

背景

功能性消化不良（FD）是一种多因素疾病。与幽门螺杆菌（H. pylori）相关的消化不良（HpD）可能被视为一种独立的实体。十二指肠嗜酸性粒细胞增多是 FD 的潜在发病机制。然而，十二指肠嗜酸性粒细胞增多和宿主固有和促炎级联、核苷酸结合寡聚化结构域 1（NOD-1）和白细胞介素-1β（IL-1β）的遗传多态性在 HpD 中的影响尚未得到探索。

目的

评估 NOD1-796G>A 和 IL-1B-511C>T 基因变异与 HpD 中低度十二指肠嗜酸性粒细胞增多的相关性。

方法

进行了一项多中心横断面研究。在上消化道内镜检查前选择了 253 名符合罗马-IV 标准的患者，在上消化道内镜检查无异常并在胃活检中检测到阳性 H. pylori 后，纳入了 98 名患者。评估了临床参数、H. pylori cagA 和十二指肠组织学。

结果

64 名（65%）患者有上腹痛综合征（EPS），24 名（25%）餐后不适综合征（PDS），10 名（10%）EPS/PDS 重叠。FD 亚型与 NOD1-796G>A 和 IL-1B-511C>T 基因变异无关。与单 A 等位基因相比，NOD1-796 GG 中的低度十二指肠嗜酸性粒细胞增多显著增加，但 IL-1B-511 单 T 等位基因或 CC 等位基因则不然。这种关联依赖于 cagA 感染，因为携带 cagA 株与 NOD1-796 GG 中的孤立变异和 IL-1B-511 单 T 等位基因相关的低度十二指肠嗜酸性粒细胞增多显著相关，但与 cagA 无关。当我们在 HpD 中对 NOD1-796 GG/IL-1B-511 单 T-allele 进行联合多态性分析时，发现这两个位点之间存在低度十二指肠嗜酸性粒细胞增多的协同作用，无论 cagA 株的状态如何。