Assessment of the toll-like receptor 4 Asp299Gly, Thr399Ile and interleukin-8 -251 polymorphisms in the risk for the development of distal gastric cancer.
Assessment of the toll-like receptor 4 Asp299Gly, Thr399Ile and interleukin-8 -251 polymorphisms in the risk for the development of distal gastric cancer.
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DOI：
10.1186/1471-2407-7-70
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发表时间：
2007-04-26
期刊：
影响因子：
3.8
通讯作者：
Perez-Perez GI
中科院分区：
文献类型：
--
作者：
Garza-Gonzalez E;Bosques-Padilla FJ;Mendoza-Ibarra SI;Flores-Gutierrez JP;Maldonado-Garza HJ;Perez-Perez GI
幽门螺杆菌定植引起的炎症反应强度与远端胃癌的发生有关。宿主对H.幽门螺杆菌与影响先天性和适应性免疫应答的遗传多态性有关。我们的目的是调查是否存在TLR 4 Asp 299 Gly，TLR 4 Thr 399 Ile和IL-8-251 A/T多态性在墨西哥人群远端GC的发展有任何影响。我们研究了337例患者，分为两组：78例经组织学证实的远端GC和259例非癌症对照。H.对照人群中的幽门螺杆菌通过四种诊断测试中至少两种的阳性结果来定义：血清学、组织学、快速尿素酶测试和培养。纯化人DNA，并通过焦磷酸测序对TLR 4 Asp 299 Gly多态性进行基因分型，通过PCR-RFLP对TLR 4 Thr 399 Ile进行基因分型，通过扩增难治性突变系统（ARMS）-PCR对IL 8 -251进行基因分型。发现非癌症对照组在所研究的多态性基因座处处于Hardy-Weinberg平衡（IL 8 -251的卡方H-W = 0.58，TLR 4 Asp 299 Gly的卡方H-W = 0.42，TLR 4 Thr 399 Ile的卡方H-W = 0.17）。比较病例组和对照组的突变等位基因（纯合子加杂合子）频率。我们发现TLR 4-Asp 299 Gly [7.7%的远端GC患者和7.7%的非癌症对照（p = 0.82）]和TLR 4 Thr 399 Ile [1.3%的GC患者和5%的对照群体（p = 0.2）]没有显著差异。相比之下，对于IL-8-251 A/T，80.77%的GC患者和66.4%的年龄和性别匹配的对照组具有至少一个拷贝的突变等位基因（OR = 2.12，95%CI = 1.1-4.2）（p = 0.023）。这项研究表明，IL 8 -251*A等位基因可能与墨西哥人群远端胃癌的发生有关。
The intensity of the inflammation induced by Helicobacter pylori colonization is associated with the development of distal gastric cancer (GC). The host response to H. pylori has been related to genetic polymorphisms that influence both innate and adaptive immune responses. Our aim was to investigate whether the presence of the TLR4 Asp299Gly, TLR4 Thr399Ile and IL-8-251 A/T polymorphisms had any influence in the development of distal GC in a Mexican population. We studied 337 patients that were divided in two groups: 78 patients with histologically confirmed distal GC and 259 non-cancer controls. The presence of H. pylori in the control population was defined by positive results of at least two of four diagnostic tests: serology, histology, rapid urease test and culture. Human DNA was purified and genotyped for TLR4 Asp299Gly polymorphism by pyrosequencing, for TLR4 Thr399Ile by PCR-RFLP and for IL8-251 by the amplification refractory mutation system (ARMS)-PCR. The non-cancer control group was found to be in Hardy-Weinberg equilibrium at the polymorphic loci studied (chi-square H-W = 0.58 for IL8-251, 0.42 for TLR4 Asp299Gly and 0.17 for TLR4 Thr399Ile). The frequencies of mutated alleles (homozygous plus heterozygous) were compared between cases and controls. We found no significant difference for TLR4- Asp299Gly [the 7.7% of distal GC patients and 7.7 % non-cancer controls (p = 0.82)] and for TLR4 Thr399Ile [the 1.3% of GC patients and the 5% of the control population (p = 0.2)]. In contrast, for IL-8-251 A/T, 80.77% of the GC patients and 66.4% in the control group age and gender matched had at least one copy of mutated allele (OR = 2.12, 95% CI = 1.1–4.2) (p = 0.023). This study showed that the IL8-251*A allele could be related to the development of distal gastric cancer in this Mexican population.
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