兒童幽門桿菌感染的免疫基因多型性研究

The genetic polymorphisms of immunity in children with Helicobacter pylori infection

陳思達(Szu-Ta Chen)

指導教授 ： 倪衍玄

國立臺灣大學/醫學院/臨床醫學研究所/碩士(2013年)

https://doi.org/10.6342/NTU.2013.01717

摘要

研究背景: 幽門桿菌感染是胃潰瘍、十二指腸潰瘍、胃癌和胃淋巴癌的重要影響因子，也是重要的致癌物。幽門桿菌感染主要發生在兒童時期，從雙胞胎研究文獻中發現幽門桿菌感染會受到基因影響(genetic effects)，遺傳率(Heritability)估計為0.57-0.67。研究發現幽門桿菌感染和宿主胃部的免疫反應失效有關，免疫相關基因及ABO基因多型性(single nucleotide polymorphism, SNP)是否會影響兒童期幽門桿菌感染的易感性(genetic susceptability)，目前仍不清楚。
研究目的:本研究納入10-18歲的兒童，探討比較有幽門桿菌感染和無幽門桿菌感染(對照組)兒童，免疫反應相關基因(IL-1B, IL-8, IL-10)及ABO基因的多型性，以了解兒童期幽門桿菌感染是否存在基因易感性。
研究方法: 本研究在雲林地區經由醫院、社區和學校收案，依照血清免疫試驗(serology test)有無幽門桿菌感染抗體分為2組:(1)實驗組為陽性; (2)對照組為陰性。檢驗血液生化學檢查，以及利用real-time PCR genotyping assay檢測5個基因的SNPs IL-1B-31 (rs1143627)、IL-1B-511 (rs16944)、IL-8-251 (rs4073)、 IL-10-1082 (rs1800896)及ABO (rs505922)，比較實驗組與對照組之間的差異。
研究結果: 全部共644位兒童納入本研究，平均年齡為14.0歲，整體幽門桿菌血清陽性率為10.7%。幽門桿菌陽性兒童的年齡較高(P = 0.0195)且血液中鐵(ferrum)較低(P = 0.005)，但ferritin沒有顯著差異。多變數分析後，在陽性兒童中，發現IL-1B-31(rs1143627)基因的T allele比率顯著比對照組低(OR = 0.846, 95% CI = 0.012 - 0.067, P = 0.014)，而在ABO (rs505922)基因的T allele比率顯著比對照組高(OR = 6.128, 95% CI = 2.381 - 15.769, P < 0.001)，而其他幾個基因的SNPs IL-1B-511、IL-8-251及IL-10-1082則在兩組間沒有差異。
結論: 雲林地區青少年兒童幽門桿菌感染血清陽性率為10.7%，陽性兒童血液中鐵濃度較低。帶有ABO (rs505922)基因的T allele的兒童具有幽門桿菌感染的易感性(susceptability)，而帶有IL-1B-31(rs1143627) T allele的兒童，則較不具幽門桿菌感染的易感性(susceptability)。

關鍵字

幽門桿菌 ； 基因多型性

並列摘要

Background: H. pylori is a major pathogen of chronic antral gastritis, peptic ulcer disease, gastric cancer, and gastric B-cell lymphoma. Acquisition of H. pylori infection predominantly occurs during childhood period. Twin studies revealed that the genetic effects might influence the H. pylori infection, with an estimated heritability of 0.57 to 0.67. The success of H. pylori infection is related with the failure of host immune responses. However, the association between host immune gene single nucleotide polymorphisms (SNP) and the susceptability of H. pylori infection is not well understood.

Study aim: We aim to study the genetic polymorphisms of immune response genes (IL-1B, IL-8, and IL-10) and ABO gene between 10 to 18 year-old children with or without H. pylori infection and to understand the genetic susceptability in childhood H. pylori infection .

Materials and methods: Subjects in this study were enrolled from schools, community, or the NTU hospital YunLin branch in YunLin county. Children with major systemic disorders or psychological disorders will be excluded. Based on the serology test result of anti- H. pylori IgG, children were divided into 2 groups: (1) study group with positive infection; (2) control group with negative infection. Biochemistry tests were recorded. The genetic polymorphisms of 5 SNPs of IL-1B-31 (rs1143627), IL-1B-511 (rs16944), IL-8-251 (rs4073), IL-10-1082 (rs1800896), and ABO gene (rs505922) were examined by a real-time PCR genotyping assay. The results were compared between 2 groups.

Results: A total 644 children were enrolled in this study with an average age of 14.0 years. The overall seroprevalence rate of H. pylori was 10.7%. The age was significantly higher and the serum ferrum level was significantly lower in children with positive infection than negative infection (P = 0.0195 and 0.005, respectively). By multivariate analysis, the T allele frequency of IL-1B-31 SNP (rs1143627) was significantly lower in seropositive children than control group (OR = 0.846, 95% CI = 0.012 - 0.067, P = 0.014). The T allele frequency of ABO SNP (rs505922) was significantly higher in seropositive children (OR = 6.128, 95% CI = 2.381 - 15.769, P < 0.001).

Conclusions: The seroprevalence rate of H. pylori infection was estimated 10.7% in adolescence in Yunlin county. Children with T allele of ABO SNP (rs505922) might be susceptible to H. pylori infection, and those with T allele of IL-1B-31 SNP (rs1143627) might be resistant to H. pylori infection.

並列關鍵字

H. pylori ； single nucleotide polymorphism

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