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Epiregulin (EREG) and human V-ATPase (TCIRG1): genetic variation, ethnicity and pulmonary tuberculosis susceptibility in Guinea-Bissau and The Gambia

Genes & Immunity volume 15, pages 370–377 (2014)Cite this article

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Abstract

We analyzed two West African samples (Guinea-Bissau: n=289 cases and 322 controls; The Gambia: n=240 cases and 248 controls) to evaluate single-nucleotide polymorphisms (SNPs) in Epiregulin (EREG) and V-ATPase (T-cell immune regulator 1 (TCIRG1)) using single and multilocus analyses to determine whether previously described associations with pulmonary tuberculosis (PTB) in Vietnamese and Italians would replicate in African populations. We did not detect any significant single locus or haplotype associations in either sample. We also performed exploratory pairwise interaction analyses using Visualization of Statistical Epistasis Networks (ViSEN), a novel method to detect only interactions among multiple variables, to elucidate possible interaction effects between SNPs and demographic factors. Although we found no strong evidence of marginal effects, there were several significant pairwise interactions that were identified in either the Guinea-Bissau or the Gambian samples, two of which replicated across populations. Our results indicate that the effects of EREG and TCIRG1 variants on PTB susceptibility, to the extent that they exist, are dependent on gene–gene interactions in West African populations as detected with ViSEN. In addition, epistatic effects are likely to be influenced by inter- and intra-population differences in genetic or environmental context and/or the mycobacterial lineages causing disease.

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Acknowledgements

This work was supported by the Medical Research Council (MRC UK) award G0000690 to GS and by grants from the Danish Medical Research Council, the Danish Society of Respiratory Medicine and the Danish Council of Development Research to CW and LJØ. MJW and SMW were partially supported by NIH Grant P20 GM103534.

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Authors and Affiliations

  1. Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA

    M J White

  2. Department of Genetics and Institute of Quantitative Biomedical Sciences, Dartmouth College, Hanover, NH, USA

    M J White, J S Chen, T Hu, J H Moore & S M Williams

  3. Centro di Ricerca, Ospedale San Pietro Fatebenefratelli, Rome, Italy

    A Tacconelli, G Novelli & G Sirugo

  4. Bandim Health Project, Danish Epidemiology Science Centre and Statens Serum Institute, Bissau, Guinea-Bissau

    C Wejse & V F Gomes

  5. Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark

    C Wejse & L J Østergaard

  6. Center for Global Health, School of Public Health, Aarhus University, Skejby, Denmark

    C Wejse

  7. Centre for International Health, University of Otago School of Medicine, Dunedin, New Zealand

    P C Hill

  8. MRC Laboratories, Fajara, The Gambia

    P C Hill

  9. Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, TN, USA

    D R Velez-Edwards

  10. Institute for Medicine and Public Health, Vanderbilt University, Nashville, TN, USA

    D R Velez-Edwards

  11. Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA

    D R Velez-Edwards

  12. Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA

    D R Velez-Edwards

  13. Dipartimento di Biomedicina e Prevenzione, Sezione di Genetica, Università di Roma ‘Tor Vergata’, Rome, Italy

    G Novelli

  14. Dr John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA

    W K Scott

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  1. M J White
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Correspondence to S M Williams or G Sirugo.

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White, M., Tacconelli, A., Chen, J. et al. Epiregulin (EREG) and human V-ATPase (TCIRG1): genetic variation, ethnicity and pulmonary tuberculosis susceptibility in Guinea-Bissau and The Gambia. Genes Immun 15, 370–377 (2014). https://doi.org/10.1038/gene.2014.28

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