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

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

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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.

Original languageEnglish
Pages (from-to)925-929
Number of pages5
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume22
Issue number6
DOIs
Publication statusPublished - 01-01-2007

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Toll-Like Receptor 2
Genetic Polymorphisms
Ulcerative Colitis
Colitis
Steroids
Phenotype
Polymerase Chain Reaction
Innate Immunity
Restriction Fragment Length Polymorphisms
Genes
Healthy Volunteers
Hospitalization
Alleles
Mutation
Population

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

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. / Genetic polymorphisms of CD14 and Toll-like receptor-2 (TLR2) in patients with ulcerative colitis. In: Journal of Gastroenterology and Hepatology (Australia). 2007 ; Vol. 22, No. 6. pp. 925-929.
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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.",
author = "Fangyu Wang and Tomomitsu Tahara and Tomiyasu Arisawa and Tomoyuki Shibata and Masakatsu Nakamura and Hiroshi Fujita and Masami Iwata and Yoshio Kamiya and Mitsuo Nagasaka and Kazuya Takahama and Makoto Watanabe and Ichiro Hirata and Hiroshi Nakano",
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Wang, F, Tahara, T, Arisawa, T, Shibata, T, Nakamura, M, Fujita, H, Iwata, M, Kamiya, Y, Nagasaka, M, Takahama, K, Watanabe, M, Hirata, I & Nakano, H 2007, 'Genetic polymorphisms of CD14 and Toll-like receptor-2 (TLR2) in patients with ulcerative colitis', Journal of Gastroenterology and Hepatology (Australia), vol. 22, no. 6, pp. 925-929. https://doi.org/10.1111/j.1440-1746.2007.04909.x

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

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 22, No. 6, 01.01.2007, p. 925-929.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic polymorphisms of CD14 and Toll-like receptor-2 (TLR2) in patients with ulcerative colitis

AU - Wang, Fangyu

AU - Tahara, Tomomitsu

AU - Arisawa, Tomiyasu

AU - Shibata, Tomoyuki

AU - Nakamura, Masakatsu

AU - Fujita, Hiroshi

AU - Iwata, Masami

AU - Kamiya, Yoshio

AU - Nagasaka, Mitsuo

AU - Takahama, Kazuya

AU - Watanabe, Makoto

AU - Hirata, Ichiro

AU - Nakano, Hiroshi

PY - 2007/1/1

Y1 - 2007/1/1

N2 - 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.

AB - 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.

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