Association study of common genetic variants in pre-microRNAs in patients with ulcerative colitis

Masaaki Okubo, Tomomitsu Tahara, Tomoyuki Shibata, Hiromi Yamashita, Masakatsu Nakamura, Daisuke Yoshioka, Joh Yonemura, Yoshio Kamiya, Takamitsu Ishizuka, Yoshihito Nakagawa, Mitsuo Nagasaka, Masami Iwata, Hideto Yamada, Ichiro Hirata, Tomiyasu Arisawa

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Abstract

Background: Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human diseases. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre-miRNAs (miR-196a2, miR-146a, and miR-499) with the risk of ulcerative colitis (UC) in a Japanese population. Methods: The rs11614913 (T>C), rs2910164 (C>G), and rs3746444 (A>G) SNPs were genotyped in 170 UC and 403 control subjects. Results: The rs3746444 AG genotype was significantly higher among the UC group (odds ratio (OR)=1.51, 95% CI=1.03-2.21, p=0.037). The rs3746444 AG genotype was associated with onset at an older age (OR=1.70, 95% CI=1.04-2.78, p=0.035), left-sided colitis and pancolitis (left-sided colitis, OR=2.10, 95% CI=1.12-3.94, p=0.024; pancolitis, OR=1.81, 95% CI=1.09-3.01, p=0.028, left-sided colitis+pancolitis, OR=1.91, 95% CI=1.26-2.92, p=0.003), higher number of times hospitalized (OR=2.63, 95% CI=1.22-5.69, p=0.017), steroid dependence (OR=2.63, 95% CI=1.27-5.44, p=0.014), and refractory phenotypes (OR=2.76, 95% CI=1.46-5.21, p=0.002) while the rs3746444 AA genotype was inversely associated with the number of times hospitalized (2∼, OR=0.36, 95% CI=0.17-0.79, p=0.012), steroid dependence (OR=0.42, 95% CI=0.21-0.88, p=0.021), and refractory phenotypes (OR=0.38, 95% CI=0.20-0.72, p=0.003). The rs1161913 TT genotype also held a significantly higher risk of refractory phenotype (T/T vs. T/C+C/C, OR=2.21, 95% CI=1.17-4.18, p=0.016). Conclusions: Our results provided the first evidence that rs3746444 SNP may influence the susceptibility to UC, and both rs3746444 and rs11614913 SNPs may influence the pathophysiological features of UC.

Original languageEnglish
Pages (from-to)69-73
Number of pages5
JournalJournal of Clinical Immunology
Volume31
Issue number1
DOIs
Publication statusPublished - 01-02-2011

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Genetic Association Studies
MicroRNAs
Ulcerative Colitis
Odds Ratio
Single Nucleotide Polymorphism
Colitis
Genotype
Phenotype
Steroids
Age of Onset

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Okubo, Masaaki ; Tahara, Tomomitsu ; Shibata, Tomoyuki ; Yamashita, Hiromi ; Nakamura, Masakatsu ; Yoshioka, Daisuke ; Yonemura, Joh ; Kamiya, Yoshio ; Ishizuka, Takamitsu ; Nakagawa, Yoshihito ; Nagasaka, Mitsuo ; Iwata, Masami ; Yamada, Hideto ; Hirata, Ichiro ; Arisawa, Tomiyasu. / Association study of common genetic variants in pre-microRNAs in patients with ulcerative colitis. In: Journal of Clinical Immunology. 2011 ; Vol. 31, No. 1. pp. 69-73.
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title = "Association study of common genetic variants in pre-microRNAs in patients with ulcerative colitis",
abstract = "Background: Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human diseases. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre-miRNAs (miR-196a2, miR-146a, and miR-499) with the risk of ulcerative colitis (UC) in a Japanese population. Methods: The rs11614913 (T>C), rs2910164 (C>G), and rs3746444 (A>G) SNPs were genotyped in 170 UC and 403 control subjects. Results: The rs3746444 AG genotype was significantly higher among the UC group (odds ratio (OR)=1.51, 95{\%} CI=1.03-2.21, p=0.037). The rs3746444 AG genotype was associated with onset at an older age (OR=1.70, 95{\%} CI=1.04-2.78, p=0.035), left-sided colitis and pancolitis (left-sided colitis, OR=2.10, 95{\%} CI=1.12-3.94, p=0.024; pancolitis, OR=1.81, 95{\%} CI=1.09-3.01, p=0.028, left-sided colitis+pancolitis, OR=1.91, 95{\%} CI=1.26-2.92, p=0.003), higher number of times hospitalized (OR=2.63, 95{\%} CI=1.22-5.69, p=0.017), steroid dependence (OR=2.63, 95{\%} CI=1.27-5.44, p=0.014), and refractory phenotypes (OR=2.76, 95{\%} CI=1.46-5.21, p=0.002) while the rs3746444 AA genotype was inversely associated with the number of times hospitalized (2∼, OR=0.36, 95{\%} CI=0.17-0.79, p=0.012), steroid dependence (OR=0.42, 95{\%} CI=0.21-0.88, p=0.021), and refractory phenotypes (OR=0.38, 95{\%} CI=0.20-0.72, p=0.003). The rs1161913 TT genotype also held a significantly higher risk of refractory phenotype (T/T vs. T/C+C/C, OR=2.21, 95{\%} CI=1.17-4.18, p=0.016). Conclusions: Our results provided the first evidence that rs3746444 SNP may influence the susceptibility to UC, and both rs3746444 and rs11614913 SNPs may influence the pathophysiological features of UC.",
author = "Masaaki Okubo and Tomomitsu Tahara and Tomoyuki Shibata and Hiromi Yamashita and Masakatsu Nakamura and Daisuke Yoshioka and Joh Yonemura and Yoshio Kamiya and Takamitsu Ishizuka and Yoshihito Nakagawa and Mitsuo Nagasaka and Masami Iwata and Hideto Yamada and Ichiro Hirata and Tomiyasu Arisawa",
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Okubo, M, Tahara, T, Shibata, T, Yamashita, H, Nakamura, M, Yoshioka, D, Yonemura, J, Kamiya, Y, Ishizuka, T, Nakagawa, Y, Nagasaka, M, Iwata, M, Yamada, H, Hirata, I & Arisawa, T 2011, 'Association study of common genetic variants in pre-microRNAs in patients with ulcerative colitis', Journal of Clinical Immunology, vol. 31, no. 1, pp. 69-73. https://doi.org/10.1007/s10875-010-9461-y

Association study of common genetic variants in pre-microRNAs in patients with ulcerative colitis. / Okubo, Masaaki; Tahara, Tomomitsu; Shibata, Tomoyuki; Yamashita, Hiromi; Nakamura, Masakatsu; Yoshioka, Daisuke; Yonemura, Joh; Kamiya, Yoshio; Ishizuka, Takamitsu; Nakagawa, Yoshihito; Nagasaka, Mitsuo; Iwata, Masami; Yamada, Hideto; Hirata, Ichiro; Arisawa, Tomiyasu.

In: Journal of Clinical Immunology, Vol. 31, No. 1, 01.02.2011, p. 69-73.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association study of common genetic variants in pre-microRNAs in patients with ulcerative colitis

AU - Okubo, Masaaki

AU - Tahara, Tomomitsu

AU - Shibata, Tomoyuki

AU - Yamashita, Hiromi

AU - Nakamura, Masakatsu

AU - Yoshioka, Daisuke

AU - Yonemura, Joh

AU - Kamiya, Yoshio

AU - Ishizuka, Takamitsu

AU - Nakagawa, Yoshihito

AU - Nagasaka, Mitsuo

AU - Iwata, Masami

AU - Yamada, Hideto

AU - Hirata, Ichiro

AU - Arisawa, Tomiyasu

PY - 2011/2/1

Y1 - 2011/2/1

N2 - Background: Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human diseases. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre-miRNAs (miR-196a2, miR-146a, and miR-499) with the risk of ulcerative colitis (UC) in a Japanese population. Methods: The rs11614913 (T>C), rs2910164 (C>G), and rs3746444 (A>G) SNPs were genotyped in 170 UC and 403 control subjects. Results: The rs3746444 AG genotype was significantly higher among the UC group (odds ratio (OR)=1.51, 95% CI=1.03-2.21, p=0.037). The rs3746444 AG genotype was associated with onset at an older age (OR=1.70, 95% CI=1.04-2.78, p=0.035), left-sided colitis and pancolitis (left-sided colitis, OR=2.10, 95% CI=1.12-3.94, p=0.024; pancolitis, OR=1.81, 95% CI=1.09-3.01, p=0.028, left-sided colitis+pancolitis, OR=1.91, 95% CI=1.26-2.92, p=0.003), higher number of times hospitalized (OR=2.63, 95% CI=1.22-5.69, p=0.017), steroid dependence (OR=2.63, 95% CI=1.27-5.44, p=0.014), and refractory phenotypes (OR=2.76, 95% CI=1.46-5.21, p=0.002) while the rs3746444 AA genotype was inversely associated with the number of times hospitalized (2∼, OR=0.36, 95% CI=0.17-0.79, p=0.012), steroid dependence (OR=0.42, 95% CI=0.21-0.88, p=0.021), and refractory phenotypes (OR=0.38, 95% CI=0.20-0.72, p=0.003). The rs1161913 TT genotype also held a significantly higher risk of refractory phenotype (T/T vs. T/C+C/C, OR=2.21, 95% CI=1.17-4.18, p=0.016). Conclusions: Our results provided the first evidence that rs3746444 SNP may influence the susceptibility to UC, and both rs3746444 and rs11614913 SNPs may influence the pathophysiological features of UC.

AB - Background: Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human diseases. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre-miRNAs (miR-196a2, miR-146a, and miR-499) with the risk of ulcerative colitis (UC) in a Japanese population. Methods: The rs11614913 (T>C), rs2910164 (C>G), and rs3746444 (A>G) SNPs were genotyped in 170 UC and 403 control subjects. Results: The rs3746444 AG genotype was significantly higher among the UC group (odds ratio (OR)=1.51, 95% CI=1.03-2.21, p=0.037). The rs3746444 AG genotype was associated with onset at an older age (OR=1.70, 95% CI=1.04-2.78, p=0.035), left-sided colitis and pancolitis (left-sided colitis, OR=2.10, 95% CI=1.12-3.94, p=0.024; pancolitis, OR=1.81, 95% CI=1.09-3.01, p=0.028, left-sided colitis+pancolitis, OR=1.91, 95% CI=1.26-2.92, p=0.003), higher number of times hospitalized (OR=2.63, 95% CI=1.22-5.69, p=0.017), steroid dependence (OR=2.63, 95% CI=1.27-5.44, p=0.014), and refractory phenotypes (OR=2.76, 95% CI=1.46-5.21, p=0.002) while the rs3746444 AA genotype was inversely associated with the number of times hospitalized (2∼, OR=0.36, 95% CI=0.17-0.79, p=0.012), steroid dependence (OR=0.42, 95% CI=0.21-0.88, p=0.021), and refractory phenotypes (OR=0.38, 95% CI=0.20-0.72, p=0.003). The rs1161913 TT genotype also held a significantly higher risk of refractory phenotype (T/T vs. T/C+C/C, OR=2.21, 95% CI=1.17-4.18, p=0.016). Conclusions: Our results provided the first evidence that rs3746444 SNP may influence the susceptibility to UC, and both rs3746444 and rs11614913 SNPs may influence the pathophysiological features of UC.

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