Erzin Yusuf, Koksal Vedat, Altun Sibel, Dobrucali Ahmet, Aslan Mustafa, Erdamar Sibel, Goksel Süha, Dirican Ahmet, Kocazeybek Bekir
Department of Gastroenterology, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey.
J Gastroenterol. 2008;43(9):705-10. doi: 10.1007/s00535-008-2220-7. Epub 2008 Sep 20.
Helicobacter pylori infection leads to different clinical outcomes depending on both host and bacterial factors. In a recent study, we identified H. pylori cagE and babA2 genotypes as independent predictors of duodenal ulcer (DU) and gastric cancer (GC) in dyspepsia patients, but no previous studies have examined the role of host-related genetic factors in Turkey. This time our aim was to evaluate whether polymorphisms of the interleukin 1B (IL-1B) and the interleukin 1 receptor antagonist (IL-1RN) genes are important factors in the differential expression of gastroduodenal diseases in H. pylori-positive dyspepsia patients.
Ninety-three H. pylori-positive patients, 30 with nonulcer dyspepsia (NUD), 30 with DU, and 33 with GC, were investigated. The IL-1B-511 and IL-1B-31 biallelic polymorphisms, and the IL-1RN intron 2 variable number tandem repeat were genotyped by polymerase chain reaction and single-strand confirmation polymorphism analysis.
The IL-1RN-1/1 genotype was significantly more prevalent among patients with NUD than among those with GC (chi(2) = 9.270; P = 0.002), and the IL-1RN-1/2 genotype was significantly more common in patients with GC (chi(2) = 6.01; P = 0.014). Multivariate regression analysis showed that cagE, babA2, and IL-1RN-1/2 genotypes were independent predictors of GC, but when patients with benign disorders were grouped together (NUD + DU) and compared with patients with GC, regression analysis disclosed that babA2 (P = 0.000) and IL-1B-31 gene polymorphisms (CC or CT) (P = 0.01) were the only independent markers of GC.
When analyzed together with host genetic factors, the well established bacterial risk factor babA2 seems to be the most important predictor of malignant disorders, and the presence of the IL-1B-31TT genotype emerges as a protective factor against them.
幽门螺杆菌感染会导致不同的临床结果,这取决于宿主和细菌因素。在最近的一项研究中,我们确定幽门螺杆菌cagE和babA2基因型是消化不良患者十二指肠溃疡(DU)和胃癌(GC)的独立预测因子,但此前尚无研究探讨土耳其宿主相关遗传因素的作用。此次我们的目的是评估白细胞介素1B(IL-1B)和白细胞介素1受体拮抗剂(IL-1RN)基因的多态性是否是幽门螺杆菌阳性消化不良患者胃十二指肠疾病差异表达的重要因素。
对93例幽门螺杆菌阳性患者进行了研究,其中30例为非溃疡性消化不良(NUD),30例为DU,33例为GC。通过聚合酶链反应和单链构象多态性分析对IL-1B -511和IL-1B -31双等位基因多态性以及IL-1RN内含子2可变数目串联重复序列进行基因分型。
IL-1RN -1/1基因型在NUD患者中比在GC患者中显著更常见(χ² = 9.270;P = 0.002),而IL-1RN -1/2基因型在GC患者中显著更常见(χ² = 6.01;P = 0.014)。多变量回归分析显示,cagE、babA2和IL-1RN -1/2基因型是GC的独立预测因子,但当将良性疾病患者归为一组(NUD + DU)并与GC患者进行比较时,回归分析显示babA2(P = 0.000)和IL-1B -31基因多态性(CC或CT)(P = 0.01)是GC的唯一独立标志物。
与宿主遗传因素一起分析时,已确定的细菌危险因素babA2似乎是恶性疾病最重要的预测因子,而IL-1B -31TT基因型的存在则是针对这些疾病的保护因素。