Assis Shirleide, Marques Cintia Rodrigues, Silva Thiago Magalhães, Costa Ryan Santos, Alcantara-Neves Neuza Maria, Barreto Mauricio Lima, Barnes Kathleen Carole, Figueiredo Camila Alexandrina
Instituto de Ciências da Saúde, UFBa, Salvador, Brazil.
Helicobacter. 2014 Jun;19(3):168-73. doi: 10.1111/hel.12119. Epub 2014 Mar 17.
Helicobacter pylori infection is a strong risk factor for gastric cancer, likely due to the extensive inflammation in the stomach mucosa caused by these bacteria. Many studies have reported an association between IL10 polymorphisms, the risk of gastric cancer, and IL-10 production. The aim of the study was to evaluate the association between IL10 genetic variants, Helicobacter pylori infection, and IL-10 production by peripheral blood leukocytes in children.
We genotyped a total of 12 single nucleotide polymorphisms in IL10 in 1259 children aged 4-11 years living in a poor urban area in Salvador, Brazil, using TaqMan probe based, 5' nuclease assay minor groove binder chemistry. Association tests were performed by logistic regression for Helicobacter pylori infection and linear regression for IL-10 spontaneous production (whole-blood cultures) including sex, age, and principal components for informative ancestry markers as covariates, using PLINK.
Our results shown that IL10 single nucleotide polymorphisms rs1800896 (OR = 1.63; 95% CI = 1.11-2.39), rs3024491 (OR = 1.71; 95% CI = 1.14-2.57), rs1878672 (OR = 1.79; 95% CI = 1.19-2.68), and rs3024496 (OR = 1.48; 95% CI = 1.05-2.08) were positively associated with Helicobacter pylori infection. Eight single nucleotide polymorphisms were associated with spontaneous production of IL-10 in culture, of which three (rs1800896 and rs1878672, p = .04; rs3024491, p = .01) were strongly associated with infection by Helicobacter pylori.
Our results indicate that IL10 variants rs1800896, rs3024491, rs1878672, and rs3024496 are more consistently associated with the presence of anti-H. pylori IgG by inducing increased production of IL-10. Further studies are underway to elucidate the role of additional genetic variants and to investigate their impact on the occurrence of gastric cancer.
幽门螺杆菌感染是胃癌的一个重要危险因素，可能是由于这些细菌引起胃黏膜广泛炎症所致。许多研究报告了白细胞介素10（IL10）基因多态性、胃癌风险与IL-10产生之间的关联。本研究的目的是评估儿童中IL10基因变异、幽门螺杆菌感染与外周血白细胞产生IL-10之间的关联。
我们采用基于TaqMan探针的5'核酸酶检测小沟结合剂化学方法，对巴西萨尔瓦多一个贫困市区1259名4至11岁儿童的IL10基因中的12个单核苷酸多态性进行了基因分型。使用PLINK软件进行关联测试，对幽门螺杆菌感染采用逻辑回归分析，对IL-10自发产生（全血培养）采用线性回归分析，将性别、年龄和信息性祖先标记的主成分作为协变量。
我们的结果显示，IL10单核苷酸多态性rs1800896（比值比[OR]=1.63；95%置信区间[CI]=1.11-2.39）、rs3024491（OR=1.71；95%CI=1.14-2.57）、rs1878672（OR=1.79；95%CI=1.19-2.68）和rs3024496（OR=1.48；95%CI=1.05-2.08）与幽门螺杆菌感染呈正相关。8个单核苷酸多态性与培养中IL-10的自发产生相关，其中3个（rs1800896和rs1878672，p=0.04；rs3024491，p=0.01）与幽门螺杆菌感染密切相关。
我们的结果表明，IL10变异体rs1800896、rs3024491、rs1878672和rs3024496通过诱导IL-10产生增加，更一致地与抗幽门螺杆菌IgG的存在相关。正在进行进一步研究以阐明其他基因变异的作用，并调查它们对胃癌发生的影响。
