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Identification of genetic associations of SP110/MYBBP1A/RELA with pulmonary tuberculosis in the Chinese Han population

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Abstract

Genetic factors play important roles in the development of tuberculosis (TB). SP110 is a promising candidate target for controlling TB infections. However, several studies associating SP110 single nucleotide polymorphisms (SNPs) with TB have yielded conflicting results. This may be partly resolved by studying other genes associated with SP110, such as MYBBP1A and RELA. Here, we genotyped 6 SP110 SNPs, 8 MYBBP1A SNPs and 5 RELA SNPs in 702 Chinese pulmonary TB patients and 425 healthy subjects using MassARRAY and SNaPshot methods. Using SNP-based analysis with Bonferroni correction, rs3809849 in MYBBP1A [Pcorrected (cor) = 0.0038] and rs9061 in SP110 (Pcor = 0.019) were found to be significantly associated with TB. Furthermore, meta-analysis of rs9061 in East Asian populations showed that the rs9061 T allele conferred significant risk for TB [P = 0.002, pooled odds ratio (OR), 1.24, 95 % confidence interval (CI) = 1.08–1.43]. The MYBBP1A GTCTTGGG haplotype and haplotypes CGACCG/TGATTG within SP110 were found to be markedly and significantly associated with TB (P = 2.00E−06, 5.00E−6 and 2.59E−4, respectively). Gene-based analysis also demonstrated that SP110 and MYBBP1A were each associated with TB (Pcor = 0.011 and 0.035, respectively). The logistic regression analysis results supported interactions between SP110 and MYBBP1A, indicating that subjects carrying a GC/CC genotype in MYBBP1A and CC genotype in SP110 possessed the high risk of developing TB (P = 1.74E−12). Our study suggests that a combination of SP110 and MYBBP1A gene polymorphisms may serve as a novel marker for identifying the risk of developing TB in the Chinese Han population.

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Acknowledgments

We thank three anonymous reviewers for their useful comments. And we are grateful to all subjects participating in this study, especially to Prof. Krzysztof Trzciński and Dr. Daniel M. Czajkowsky for their warm-hearted help and critical comments on the manuscript. This work was supported by the Chinese National Science Foundation (No. 31101015), the National Infectious Disease Prevention and Cure Special Project (No. 2008ZX10003-012) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry, China.

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All authors have no conflicts to report.

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Authors and Affiliations

  1. Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai, 200030, China

    Lei Cai, Chun-Ling Wan, Guang He & Lin He

  2. Gordon Life Science Institute, 13784 Torrey Del Mar Drive, San Diego, CA, 92130, USA

    Lei Cai & Jia Zhou

  3. Key Laboratory of Systems Biomedicine, Shanghai Centre for Systems Biomedicine, Shanghai Jiaotong University, Shanghai, China

    Lei Cai & Jia Zhou

  4. Department of Laboratory Medicine, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, China

    Shao-Li Deng

  5. Shanghai Key Laboratory of Mycobacterium Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Rd, Shanghai, 200433, China

    Li Liang & Jun Yue

  6. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, USA

    Hui Pan

  7. Fudan University School of Life Sciences and Technology, Advanced Institute of Translational Medicine, Shanghai, China

    Mei-Yan Wang

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  1. Lei Cai
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  2. Shao-Li Deng
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  8. Chun-Ling Wan
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  9. Guang He
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Correspondence to Lei Cai or Jun Yue.

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Cai, L., Deng, SL., Liang, L. et al. Identification of genetic associations of SP110/MYBBP1A/RELA with pulmonary tuberculosis in the Chinese Han population. Hum Genet 132, 265–273 (2013). https://doi.org/10.1007/s00439-012-1244-5

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  • DOI: https://doi.org/10.1007/s00439-012-1244-5

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