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Tagging Single Nucleotide Polymorphisms in the IRF1 and IRF8 Genes and Tuberculosis Susceptibility

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  • Shiping Ding
  • Tao Jiang
  • Jianqin He
  • Beibei Qin
  • Shuangyan Lin
  • Lanjuan Li

Abstract

Genes encoding IRF1 and IRF8 protein have been proposed as candidate tuberculosis susceptibility genes. In order to elucidate whether the IRF1 and IRF8 variants were associated with tuberculosis susceptibility, we conducted a case-control study consisting of 495 controls and 452 ethnically matched cases with tuberculosis in a Chinese population. Seven haplotype tagging single-nucleotide polymorphisms (tagSNPs) (rs2057656; rs2706381; rs2070724; rs2070721; rs2549008; rs2549007; rs2706386) from HapMap database were analyzed, which provided an almost complete coverage of the genetic variations in the IRF1 gene. Fifteen tagSNPs (rs12924316; rs182511; rs305080; rs2292980; rs925994; rs424971; rs16939967; rs11117415; rs4843860; rs9926411; rs8064189; rs12929551; rs10514611; rs1044873; rs6638) were observed in the IRF8 gene. All these tagSNPs were genotyped by SNPstream genotyping and SNaPshot typing. None of the seven tagSNPs was individually associated with tuberculosis in the IRF1 gene. In the IRF8 gene, interestingly, we found that three tagSNPs (rs925994 and rs11117415 located in the intron region; rs10514611 located in the 3′UTR) were associated with risk of tuberculosis after Bonferroni correction. Per allele OR was 1.75 (95% CI 1.35∼2.27, P = 0.002), 4.75 (95% CI 2.16∼10.43, P = 0.002) and 3.39 (95% CI 1.60∼7.20, P = 0.015) respectively. Luciferase reporter gene assay showed that the construct that contained the non-risk allele C of rs10514611 showed significantly higher luciferase activity than did the risk T allele (P

Suggested Citation

  • Shiping Ding & Tao Jiang & Jianqin He & Beibei Qin & Shuangyan Lin & Lanjuan Li, 2012. "Tagging Single Nucleotide Polymorphisms in the IRF1 and IRF8 Genes and Tuberculosis Susceptibility," PLOS ONE, Public Library of Science, vol. 7(8), pages 1-8, August.
    • Handle: RePEc:plo:pone00:0042104
    DOI: 10.1371/journal.pone.0042104
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    1. Kouetsu Ogasawara & Shigeaki Hida & Nazli Azimi & Yutaka Tagaya & Takeo Sato & Taeko Yokochi-Fukuda & Thomas A. Waldmann & Tadatsugu Taniguchi & Shinsuke Taki, 1998. "Requirement for IRF-1 in the microenvironment supporting development of natural killer cells," Nature, Nature, vol. 391(6668), pages 700-703, February.
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