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Synergistic contribution of CD14 and HLA loci in the susceptibility to Buerger disease

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Abstract

Buerger disease (BD) is an occulusive vascular disease of unknown etiology. Although cigarette smoking is a well-known risk factor of BD, genetic factors may also play a role in the etiology. Because chronic bacterial infection such as oral periodontitis is suggested to be involved in the pathogenesis of BD, gene polymorphisms involved in the infectious immunity might be associated with BD as the genetic factor(s). We have previously reported that HLA-DRB1*1501 and B54 was associated with BD in Japanese. In this study, polymorphisms in HLA-DPB1, DRB1 and B were analyzed in 131 Japanese BD patients and 227 healthy controls. In addition, we investigated a functional promoter polymorphism, −260 C > T, of CD14 that is a main receptor of bacterial lipopolysaccharide. It was found that the frequencies of CD14 TT genotype [37.4 vs. 24.2%, P = 0.008 OR = 1.87, 95% confidence interval (CI); 1.18, 2.97], DRB1*1501 (34.4 vs. 13.2%, P c = 4.4 × 10−5, OR = 3.44, 95%CI; 2.06, 5.73) and DPB1*0501 (79.4 vs. 55.1%, P c = 4.7 × 10−5, OR = 3.14, 95%CI; 1.93, 5.11) were significantly higher in the patients than in the controls, demonstrating that at least three genetic markers were associated with BD. Stratification analyses of these associated markers suggested synergistic roles of the genetic factors. Odds ratios ranged from 4.72 to 12.57 in individuals carrying any two of these three markers. These findings suggested that the susceptibility to BD was in part controlled by genes involved in the innate and adaptive immunity.

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Acknowledgments

This work was supported in part by grants-in-aids from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) Japan. We thank staffs in vascular surgery department of Tokyo Medical and Dental University for the sample collection.

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Authors and Affiliations

  1. Department of Vascular and Applied Surgery, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan

    Zhiyong Chen, Yoshinori Inoue & Takehisa Iwai

  2. Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo, 101-0062, Japan

    Zhiyong Chen, Megumi Takahashi, Taeko Naruse, Toshiaki Nakajima & Akinori Kimura

  3. Laboratory of Genome Diversity, School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan

    Toshiaki Nakajima & Akinori Kimura

  4. Periodontology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan

    Yi-Wen Chen & Isao Ishikawa

  5. Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Isao Ishikawa

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  1. Zhiyong Chen
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  2. Megumi Takahashi
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  3. Taeko Naruse
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  8. Takehisa Iwai
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  9. Akinori Kimura
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Correspondence to Akinori Kimura.

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Chen, Z., Takahashi, M., Naruse, T. et al. Synergistic contribution of CD14 and HLA loci in the susceptibility to Buerger disease. Hum Genet 122, 367–372 (2007). https://doi.org/10.1007/s00439-007-0408-1

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  • DOI: https://doi.org/10.1007/s00439-007-0408-1

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