Davoodi Homa, Seow Heng Fong
Department of Microbiology and Immunology, Golestan University of Medical Sciences, Gorgan, Iran.
Iran J Allergy Asthma Immunol. 2011 Jun;10(2):91-9.
The innate immune system recognizes the presence of bacterial products through the expression of a family of membrane receptors known as Toll-like receptors (TLRs). Polymorphisms in TLRs have been shown to be associated with increased susceptibility to diseases such as inflammatory bowel disease. The aim of this study was to determine whether there was a correlation between polymorphisms of TLR4 (Asp299Gly; Thr399Ile) and TLR2 (Arg677Trp; Arg753Gln) genes and risk of colorectal cancer. DNA from 60 colorectal carcinoma patients from 3 major races in Malaysia (22 Malays, 20 Chinese and 18 Indians) and blood from 50 apparently healthy individuals were evaluated. Control group were matched to study group by race and age. The polymorphisms were determined by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Genotyping results showed two out of sixty tumour specimens (3.3%) harbored both variant TLR4 Asp299Gly and Thr399Ile alleles. In contrast, DNA isolated from blood cells of 50 apparently healthy individuals harbored wild type TLR4. In the case of TLR2 Arg753Gln genotyping, all of the fifty normal and 60 tumours were of the wild type genotype. TLR2 Arg677Trp genotyping showed a heterozygous pattern in all samples. However, this may not be a true polymorphism of the TLR2 gene as it is likely due to a variation of a duplicated ( pseudogene) region. There was only a low incidence (2/60; 3.3%) of TLR4 polymorphism at the Asp299Gly and Thr399Ile alleles in colorectal cancer patients. All normal and tumour samples harbored the wild type TLR2 Arg753 allele. Our study suggests that variant TLR4 (Asp299Gly and Thr399Ile alleles) as well as TLR2 (Arg753Gln allele) are not associated with risk of colorectal cancer.
天然免疫系统通过一类被称为Toll样受体（TLRs）的膜受体的表达来识别细菌产物的存在。TLRs基因多态性已被证明与炎症性肠病等疾病的易感性增加有关。本研究的目的是确定TLR4（Asp299Gly；Thr399Ile）和TLR2（Arg677Trp；Arg753Gln）基因多态性与结直肠癌风险之间是否存在相关性。对来自马来西亚3个主要种族的60例结直肠癌患者（22名马来人、20名中国人和18名印度人）的DNA以及50名明显健康个体的血液进行了评估。对照组按种族和年龄与研究组匹配。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）确定多态性。基因分型结果显示，60个肿瘤标本中有2个（3.3%）同时携带变异的TLR4 Asp299Gly和Thr399Ile等位基因。相比之下，从50名明显健康个体的血细胞中分离出的DNA携带野生型TLR4。在TLR2 Arg753Gln基因分型中，50例正常样本和60例肿瘤样本均为野生型基因型。TLR2 Arg677Trp基因分型在所有样本中均显示杂合模式。然而，这可能不是TLR2基因的真正多态性，因为它可能是由于一个重复（假基因）区域的变异。结直肠癌患者中TLR4多态性在Asp299Gly和Thr399Ile等位基因处的发生率较低（2/60；3.3%）。所有正常和肿瘤样本均携带野生型TLR2 Arg753等位基因。我们的研究表明，变异的TLR4（Asp299Gly和Thr399Ile等位基因）以及TLR2（Arg753Gln等位基因）与结直肠癌风险无关。
