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Combined Effect of miR-146a rs2910164 G/C Polymorphism and Toll-like Receptor 4 +3725 G/C Polymorphism on the Risk of Severe Gastric Atrophy in Japanese

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Abstract

Background

A G/C polymorphism in miRNA-146a (rs2910164) was shown to be associated with the risk of hepatocellular carcinoma.

Objective

This study aimed to examine the associations of the miR-146a G/C (rs2910164) and TLR4 +3725 G/C (rs11536889) polymorphisms with the risk of Helicobacter pylori (H. pylori) infection, gastric atrophy, and gastric cancer in a Japanese population.

Methods

Subjects for this study were 583 histologically diagnosed gastric cancer patients and age- and sex-frequency-matched 1,742 control outpatients (1,637 subjects were eligible for the analyses), who visited Aichi Cancer Center Hospital from the year 2001 to 2005. Serum pepsinogens were measured to evaluate gastric atrophy.

Results

When H. pylori-seropositive subjects or subjects with gastric atrophy were defined as H. pylori-infected subjects, the age- and sex-adjusted odds ratio (aOR) of severe gastric atrophy among the H. pylori infected was 1.44 (95% confidence interval [95% CI] = 0.89–2.34, p = 0.133) in G/G genotype of miR-146a polymorphism. When combined with TLR4 G/C polymorphism, the OR in those with miR-146a G/G and TLR4 G/C+C/C genotypes was significantly increased relative to those with miR-146a C/C+G/C and TLR4 G/G among the H. pylori-infected subjects: aOR = 2.04 (95% CI = 1.10–3.82, p = 0.025).

Conclusions

This study revealed the combined effect of miR-146a rs2910164 G/G and TLR4 +3725 C allele on the increased risk of severe gastric atrophy among the H. pylori-infected Japanese subjects.

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Acknowledgments

The authors wish to thank Ms. Yoko Mitsuda and all the staff involved in this study. This study was supported in part by a Grant-in-Aid for Scientific Research on Special Priority Areas of Cancer from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

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Authors and Affiliations

  1. Department of Preventive Medicine/Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Asahi Hishida, Yasuyuki Goto, Mariko Naito, Kenji Wakai & Nobuyuki Hamajima

  2. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan

    Keitaro Matsuo & Kazuo Tajima

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  1. Asahi Hishida
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  2. Keitaro Matsuo
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  3. Yasuyuki Goto
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  7. Nobuyuki Hamajima
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Correspondence to Asahi Hishida.

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Hishida, A., Matsuo, K., Goto, Y. et al. Combined Effect of miR-146a rs2910164 G/C Polymorphism and Toll-like Receptor 4 +3725 G/C Polymorphism on the Risk of Severe Gastric Atrophy in Japanese. Dig Dis Sci 56, 1131–1137 (2011). https://doi.org/10.1007/s10620-010-1376-1

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  • DOI: https://doi.org/10.1007/s10620-010-1376-1

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