Genetic polymorphisms of CD14 and Toll-like receptor-2 (TLR2) in patients with ulcerative colitis

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Journal of Gastroenterology and Hepatology

Volume 22 Issue 6 Page 925Issue 6 - 929 - June 2007

To cite this article: Fangyu Wang, Tomomitsu Tahara, Tomiyasu Arisawa, Tomoyuki Shibata, Masakatsu Nakamura, Hiroshi Fujita, Masami Iwata, Yoshio Kamiya, Mitsuo Nagasaka, Kazuya Takahama, Makoto Watanabe, Ichiro Hirata, Hiroshi Nakano (2007) Genetic polymorphisms of CD14 and Toll-like receptor-2 (TLR2) in patients with ulcerative colitis Journal of Gastroenterology and Hepatology 22 (6), 925–929. doi:10.1111/j.1440-1746.2007.04909.x

GASTROENTEROLOGY

*Department of Gastroenterology, School of Medicine, Fujita Health University, Toyoake, Japan; and Department of Gastroenterology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China

Dr Tomiyasu Arisawa, 1-98 Dengakugakubo, Kutsukake-Cho, Toyoake 470-1192, Japan. Email: tarisawa@...

Abstract

Background and Aim: 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.

Methods: 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.

Results: 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).

Conclusion: 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.