García-González María A, Aísa María A Pérez, Strunk Mark, Benito Rafael, Piazuelo Elena, Jiménez Pilar, Sopeña Federico, Lanas Angel
Instituto Aragonés de Ciencias de la Salud, Zaragoza, Spain.
Hum Immunol. 2009 Nov;70(11):935-45. doi: 10.1016/j.humimm.2009.07.024. Epub 2009 Aug 5.
We aimed to evaluate the influence of Helicobacter pylori infection and IL-1/TNF gene polymorphisms on interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha gastric mucosal production. IL-1beta and TNF-alpha levels in homogenized biopsy specimens taken from the antrum and corpus of 81 patients were measured by enzyme-linked immunosorbent assay. Genomic DNA was typed for the IL1B-511, IL1B+3954, variable number of tandem repeat (VNTR) IL1RN, TNFA-308, TNFA-238, LTA NcoI, and LTA Bsi gene polymorphisms by polymerase chain reaction, restriction fragment length polymorphism, and TaqMan assays. H. pylori infection and CagA/VacA antibody status were determined by Western blot. IL-1beta and TNF-alpha protein levels were significantly higher in the gastric antrum of patients infected with H. pylori compared with uninfected patients [9.54 (5.07-16.28) vs. 4.55 (3.69-8.28) pg IL-1beta/mg protein, p = 0.004, and 1.5 (0.7-2.71) vs. 0.63 (0.3-1.26) pg TNF-alpha/mg protein, p = 0.001]. Among H. pylori-infected individuals, carriers of the IL1RN*2 allele had significantly higher antrum mucosal IL-1beta levels than noncarriers [15.97 (9.59-26.6) vs. 10.08 (7.72-13.33), p = 0.008]. No association between gastric mucosal TNF-alpha levels and genotypes of the TNFA and LTA gene polymorphisms was reported. Our results indicate that the VNTR polymorphism of the IL1RN gene influences IL-1beta gastric mucosal production in patients infected with H. pylori.
我们旨在评估幽门螺杆菌感染及白细胞介素-1（IL-1）/肿瘤坏死因子（TNF）基因多态性对白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）胃黏膜产生的影响。采用酶联免疫吸附测定法检测了81例患者胃窦和胃体活检标本匀浆中的IL-1β和TNF-α水平。通过聚合酶链反应、限制性片段长度多态性分析和TaqMan分析对IL1B - 511、IL1B + 3954、可变数目串联重复序列（VNTR）IL1RN、TNFA - 308、TNFA - 238、LTA NcoI和LTA Bsi基因多态性进行基因分型。通过蛋白质印迹法确定幽门螺杆菌感染及细胞毒素相关蛋白A（CagA）/空泡毒素A（VacA）抗体状态。与未感染患者相比，幽门螺杆菌感染患者胃窦中的IL-1β和TNF-α蛋白水平显著更高[9.54（5.07 - 16.28）对4.55（3.69 - 8.28）pg IL-1β/ mg蛋白，p = 0.004；1.5（0.7 - 2.71）对0.63（0.3 - 1.26）pg TNF-α/ mg蛋白，p = 0.001]。在幽门螺杆菌感染个体中，IL1RN * 2等位基因携带者胃窦黏膜IL-1β水平显著高于非携带者[15.97（9.59 - 26.6）对10.08（7.72 - 13.33），p = 0.008]。未报道胃黏膜TNF-α水平与TNFA和LTA基因多态性基因型之间存在关联。我们的结果表明，IL1RN基因的VNTR多态性影响幽门螺杆菌感染患者胃黏膜中IL-1β的产生。
