Wang Fangyu, Tahara Tomomitsu, Arisawa Tomiyasu, Shibata Tomoyuki, Nakamura Masakatsu, Fujita Hiroshi, Iwata Masami, Kamiya Yoshio, Nagasaka Mitsuo, Takahama Kazuya, Watanabe Makoto, Hirata Ichiro, Nakano Hiroshi
Department of Gastroenterology, School of Medicine, Fujita Health University, Toyoake, Japan.
J Gastroenterol Hepatol. 2007 Jun;22(6):925-9. doi: 10.1111/j.1440-1746.2007.04909.x.
Ulcerative colitis (UC) is a multifactorial disease resulting from a complex interaction of genetic and environmental factors. Identifying genetic variants that alter the innate immune response is highly relevant to understanding the pathogenesis of UC. The aim of this study was to investigate the association between CD14 and Toll-like receptor-2 (TLR2) genetic polymorphisms and chronic UC in Japanese patients.
The study population consisted of 102 chronic UC patients and 146 healthy control subjects. Polymorphisms in the promoter at C-260T of CD14 gene were investigated by PCR restriction fragment length polymorphism, and -196 to -174 del of TLR2 was investigated by allele-specific PCR.
The frequencies of CD14 TT and T carrier were significantly higher in UC patients than in controls (TT: OR = 3.98, 95% CI 1.82-8.71, P = 0.0005; T carrier: OR = 2.98, 95% CI 1.47-6.01, P = 0.002). In addition, TT and T carrier were more closely associated with distal colitis phenotype (TT: OR = 7.78, 95% CI 2.14-28.28, P = 0.0007; T carrier: OR = 6.30, 95% CI 2.71-14.58, P = 0.005), onset after 20 years of age (TT: OR = 5.28, 95% CI 2.18-12.79; T carrier: OR = 3.79, 95% CI 1.67-8.59), chronic continuous type (TT: OR = 4.26, 95% CI 1.56-11.64; T carrier: OR = 3.09, 95% CI 1.33-7.82), and fewer than two hospitalizations (TT: OR = 4.44, 95% CI 1.81-10.89; T carrier: OR = 3.26, 95% CI 1.43-7.27). There was no significant difference in TLR2 -196 to -174 del/del and del/ins carrier frequencies between UC patients and healthy controls. However, these frequencies were significantly higher in steroid-dependant patients than in controls (del/del: OR = 6.08, 95% CI 1.41-26.21; del carrier: OR = 3.00, 95% CI 1.13-7.98).
The results suggest that existence of a mutation in the CD14 gene is associated with an increased susceptibility to developing UC, especially chronic continuous distal colitis phenotypes that develop after 20 years of age. Furthermore, polymorphism of TLR2 may be related to an increased risk of intensive types such as steroid-dependent patients.
溃疡性结肠炎（UC）是一种由遗传和环境因素复杂相互作用导致的多因素疾病。识别改变固有免疫反应的基因变异对于理解UC的发病机制高度相关。本研究的目的是调查日本患者中CD14和Toll样受体2（TLR2）基因多态性与慢性UC之间的关联。
研究人群包括102例慢性UC患者和146例健康对照者。采用聚合酶链反应-限制性片段长度多态性方法检测CD14基因启动子C-260T处的多态性，采用等位基因特异性聚合酶链反应检测TLR2基因-196至-174位缺失。
UC患者中CD14基因TT和T携带者的频率显著高于对照组（TT：比值比[OR]=3.98，95%可信区间[CI]1.82-8.71，P=0.0005；T携带者：OR=2.98，95%CI1.47-6.01，P=0.002）。此外，TT和T携带者与远端结肠炎表型（TT：OR=7.78，95%CI2.14-28.28，P=0.0007；T携带者：OR=6.30，95%CI2.71-14.58，P=0.005）、20岁以后发病（TT：OR=5.28，95%CI2.18-12.79；T携带者：OR=3.79，95%CI1.67-8.59）、慢性持续型（TT：OR=4.26，95%CI1.56-11.64；T携带者：OR=3.09，95%CI1.33-7.82）以及住院次数少于两次（TT：OR=4.44，95%CI1.81-10.89；T携带者：OR=3.26，95%CI1.43-7.27）的相关性更强。UC患者与健康对照者之间TLR2基因-196至-174位缺失/缺失和缺失/插入携带者频率无显著差异。然而，这些频率在依赖类固醇的患者中显著高于对照组（缺失/缺失：OR=6.08，95%CI1.41-26.21；缺失携带者：OR=3.00，95%CI1.13-7.98）。
结果表明，CD14基因存在突变与发生UC的易感性增加相关，尤其是20岁以后发生的慢性持续型远端结肠炎表型。此外，TLR2基因多态性可能与依赖类固醇等重症类型患者的风险增加有关。
