Characterization and strong risk association of TLR2 del-196 to-174 polymorphism and Helicobacter pylori and their influence on mRNA expression in gastric cancer  

作　　者：Caroline de Matos Lourenco Manoela Dias Susi Mariah Cristina Antunes do Nascimento Vilson Serafim Junior Ana Paula Simedan Vila Gabriela Helena Rodrigues-Flemming Eny Maria Goloni-Bertollo Ana Elizabete Silva Juliana Garcia de Oliveira-Cucolo 

机构地区：[1]Department of Graduate-Level Research,Sacred Heart University,Bauru,Sao Paulo 17011-970,Brazil [2]Department of Molecular Biology,Sao Josédo Rio Preto School of Medicine,Sao Josédo Rio Preto,Sao Paulo 15090-000,Brazil [3]Department of Biology,Sao Paulo State University,Sao Josédo Rio Preto,Sao Paulo 15054-000,Brazil

出　　处：《World Journal of Gastrointestinal Oncology》2020年第5期535-548,共14页世界胃肠肿瘤学杂志（英文版）（电子版）

基　　金：Supported by the Sao Paulo Research Foundation,No2013/14022-6 and No.2014/17716-1

摘　　要：BACKGROUND Toll-like receptor-2(TLR2) is responsible for recognizing Helicobacter pylori(H.pylori) and activating the immune response. Polymorphisms in TLR2 may modulate gastric carcinogenesis.AIM To evaluate whether the TLR2 19216 T/C(rs3804099) and TLR2-196 to-174 ins/del(rs111200466) polymorphisms contribute to gastric carcinogenesis in the Brazilian population, and to determine the influence of both polymorphisms and H. pylori infection on TLR2 mRNA expression.METHODS DNA was extracted from 854 peripheral blood leukocyte or gastric tissue samples[202 gastric cancer(GC), 269 chronic gastritis(CG), and 383 control/healthy(C)]and genotyped by allele-specific PCR or restriction fragment length polymorphism(RFLP)-PCR. Quantitative polymerase chain reaction by Taq Man■ assay was used to quantify TLR2 mRNA levels in fresh gastric tissues(48 GC, 36 CG, and 14 C).RESULTS Regarding the TLR2-196 to -174 polymorphism, the ins/del and del/del genotypes were associated with a higher risk of GC by comparison with the C in all of the analyzed inheritance models(codominant, dominant, recessive, overdominant and log-additive;P < 0.0001). Similarly, an increased risk was observed when comparing the GC and CG groups [codominant(P < 0.0001), dominant(P <0.0001), recessive(P = 0.0260), overdominant(P < 0.0001) and log-additive(P <0.0001)]. In contrast, TLR2 19216 T/C was associated with a protective effect in the GC group compared to the C group [dominant(P = 0.0420) and log-additive(P =0.0300)]. Regarding the association of polymorphisms with H. pylori infection,individuals infected with H. pylori and harboring the TLR2-196 to-174 ins/del polymorphism had an increased risk of gastric carcinogenesis [codominant(P =0.0120), dominant(P = 0.0051), overdominant(P = 0.0240) and log-additive(P =0.0030)], while TLR2 19216 T/C was associated with a protective effect[codominant(P = 0.0039), dominant(P < 0.0001), overdominant(P = 0.0097) and log-additive(P = 0.0021)]. TLR2 mRNA levels were significantly increased in the GC group(median RQ

关 键 词：Toll-like receptor 2 Helicobacter pylori Gastric cancer Chronic gastritis POLYMORPHISMS Gene expression 

分 类 号：R57[医药卫生—消化系统]