台灣地區幽門螺旋桿菌引起之消化性潰瘍與宿主NOD1及IL-8基因多型性的相關性探討

幽門螺旋桿菌Helocobacter pylori (H. pylori)感染消化性潰瘍的產生有關。H. pylori的感染會引起宿主的免疫反應，然而免疫反應卻無法完全清除H. pylori，反而造成宿主的細胞受損。H. pylori感染後的先天性免疫反應之一，是細菌的peptidoglycan經由type IV secretion system注入宿主細胞，被NOD1 (nucleotide-biding oligomerization domain-containing protein 1)辨識之後直接活化NF-κB，誘導胃上皮細胞分泌IL-8 (interleukin 8)。曾有研究發現NOD1 G796A和IL-8 -251 A/T的多型性會增加十二指腸潰瘍的風險，但另外的研究卻指出IL-8 -251 A/T的多型性與胃潰瘍、胃癌有關，與十二指腸潰瘍不相關。本研究的目的是了解國人NOD1 G796A以及IL-8 -251 A/T多型性與H. pylori引起之胃潰瘍和十二指腸潰瘍的相關性。本研究共收集146例胃鏡快速尿素酶檢查的檢體，利用PCR restriction fragment length polymorphism，TaqMan® SNP genotyping assays (real-time PCR)，multilocus sequence typing的方法測定宿主的NOD1 G796A以及IL-8 -251 A/T多型性。統計的結果發現研究對象中，胃潰瘍的發生與年齡有相關性，不具有性別差異；十二指腸潰瘍的發生與H. pylori感染以及性別有關，男性的罹患機率較高。H. pylori感染率沒有性別差異。基因型分析的部份，本研究發現NOD1 G796A多型性為GA或AA，IL-8 -251 T/A多型性為TA或AA時，罹患十二指腸潰瘍與H. pylori的感染有顯著相關，此相關性主要來自於男性族群。H. pylori感染且宿主基因型為NOD1 A allele時，得到十二指腸潰瘍的機率明顯高於沒有感染的GG同型合子。沒有H. pylori感染的人，即使基因型不同罹患十二指腸潰瘍的機率是沒有差異的。由此推測，具有NOD1 A allele的人感染H. pylori之後如果積極進行H. pylori的除菌治療，其罹患十二指腸潰瘍的風險應可明顯降低。然而不論病人屬於哪一種基因型，H. pylori感染都與胃潰瘍都沒有相關性。胃潰瘍的產生在本研究中與H. pylori感染、NOD1、IL-8多型性都沒有相關性，過去有學者認為H. pylori在胃內分布的位置以及胃酸分泌量將會影響胃潰瘍或十二指腸的形成，這是未來需要進一步證實的部份。

Background: H. pylori - induced inflammation is central to the pathogenesis of all H. pylori - associated diseases. The type IV secretion system of H. pylori delivers peptidoglycan into the host cells, which can then be sensed by the intracellular receptor NOD1 (nucleotide-biding oligomerization domain-containing protein 1), leading to NF-κB activation and consequent IL-8 (interleukin 8) production. It had been reported NOD1 G796A and IL-8 -251 A/T polymorphism were important in H. pylori - induced peptic ulcer. However, the results were inconclusive. The aim of this study was to evaluate the role of NOD1 G796A and IL-8 -251 A/T genetic polymorphism in the development of H. pylori -induced peptic ulcer diseases in Taiwan.Materials and Methods: 146 patients with endoscope and CLO test (Campylobacter like organism test) were enrolled in the study. NOD1 G796A and IL-8 -251 A/T polymorphism were typed by PCR restriction fragment length polymorphism, TaqMan® SNP genotyping assays (real-time PCR) and multilocus sequence typing.Results: Old age was significantly associated with gastric ulcer in our study population. Duodenal ulcer was associated with H. pylori infection and gender. The prevalence of duodenal ulcer was higher in male. The H. pylori infection rate was similar in male and in female. Male NOD1 796A carriers and male IL-8 -251A carriers significantly had higher risk of H. pylori-induced duodenal ulcer. Since the genotype distribution was similar in H. pylori-infected male and female, polymorphism and gender may be independent factors of H. pylori-induced duodenal ulcer. There was no association between the polymorphism and H. pylori-induced gastric ulcer.Conclusion: NOD1 796A carriers and IL-8 -251A carriers significantly had higher risk of H. pylori-induced duodenal ulcer in male. However, it still needs further studies to clarify whether genotype or gender-related- factor plays a major role of H. pylori-induced duodenal ulcer in advance.