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Susceptibility to Buruli ulcer is associated with the SLC11A1 (NRAMP1) D543N polymorphism

Genes & Immunity volume 7, pages 185–189 (2006)Cite this article

Abstract

Similar to other mycobacterial diseases, susceptibility to Buruli ulcer (Mycobacterium ulcerans infection) may be determined by host genetic factors. We investigated the role of SLC11A1 (NRAMP1) in Buruli ulcer because of its associations with both tuberculosis and leprosy. We enrolled 182 Buruli ulcer patients (102 with positive laboratory confirmation) and 191 healthy neighbourhood-matched controls in Ghana, and studied three polymorphisms in the SLC11A1 gene: 3′ UTR TGTG ins/del, D543N G/A, and INT4 G/C. Finger prick blood samples from study subjects were dried on filter papers (FTA) and processed. D543N was significantly associated with Buruli ulcer: the odds ratio (adjusted for gender, age, and region of the participant) of the GA genotype versus the GG genotype was 2.89 (95% confidence intervals (CI): 1.41–5.91). We conclude that a genetic polymorphism in the SLC11A1 gene plays a role in susceptibility to develop Buruli ulcer, with an estimated 13% population attributable risk.

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Acknowledgements

We thank Ilona Hospers and Irene Wiersma for the collection of samples. Furthermore, we thank the staff from the following institutions for assisting with field data collection: District Health Administration and Dunkwa Government Hospital, Dunkwa-on-Offin; St Martin's Catholic Hospital, Agroyesum; and Agogo Presbyterian Hospital, Agogo.

This research was funded by the NWO (Dutch Organisation for Scientific Research), the Jan Kornelis de Cock Foundation, and the Centers for Disease Control and Prevention.

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Authors and Affiliations

  1. Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands

    Y Stienstra, T S van der Werf & W T A van der Graaf

  2. Department of Medical Biology, University Medical Center Groningen, Groningen, The Netherlands

    E Oosterom, I M Nolte, G J te Meerman & G van der Steege

  3. St Martin's Catholic Hospital, Agroyesum, Ghana

    S Etuaful

  4. National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA

    P L Raghunathan, E A S Whitney, J W Tappero & D A Ashford

  5. Ministry of Health, National Buruli Ulcer Control Program, Accra, Ghana

    E O Ampadu & K Asamoa

  6. Dunkwa Governmental Hospital, Dunkwa, Ghana

    E Y Klutse

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  1. Y Stienstra
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  2. T S van der Werf
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  5. W T A van der Graaf
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  7. P L Raghunathan
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  8. E A S Whitney
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  10. K Asamoa
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  11. E Y Klutse
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  12. G J te Meerman
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  13. J W Tappero
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  14. D A Ashford
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  15. G van der Steege
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Corresponding author

Correspondence to Y Stienstra.

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Contribution of authors

Ymkje Stienstra helped to design the study, collected data, coordinated international cooperation, and was responsible for the preparation of the paper. Tjip van der Werf designed and supervised the study, and coordinated international cooperation. Elvira Oosterom performed the laboratory analysis. Ilja Nolte was responsible for the statistical analysis. Winette van der Graaf designed and supervised the study, and coordinated international cooperation. Samuel Etuaful contributed to data collection and its supervision. Pratima Raghunathan and Ellen Whitney-Spotts were responsible for the design of the study, data collection, and contributed to data interpretation. Edwin Ampadu and Kwame Asamoa were responsible for the international cooperation and the supervision of the field activities. Erasmus Klutse contributed to data collection and its supervision. Gerard te Meerman contributed to study methods, and interpretation of results. Jordan Tappero and David Ashford designed and supervised the study, and coordinated international cooperation. Gerrit van der Steege helped in the study design, coordinated analysis, and supervised interpretation of results. All authors helped to write the paper.

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Stienstra, Y., van der Werf, T., Oosterom, E. et al. Susceptibility to Buruli ulcer is associated with the SLC11A1 (NRAMP1) D543N polymorphism. Genes Immun 7, 185–189 (2006). https://doi.org/10.1038/sj.gene.6364281

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