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Human Genetics

, Volume 127, Issue 1, pp 65–73 | Cite as

Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans

  • Digna Rosa Velez
  • Christian Wejse
  • Martin E. Stryjewski
  • Eduardo Abbate
  • William F. Hulme
  • Jamie L. Myers
  • Rosa Estevan
  • Sara G. Patillo
  • Rikke Olesen
  • Alessandra Tacconelli
  • Giorgio Sirugo
  • John R. Gilbert
  • Carol D. Hamilton
  • William K. ScottEmail author
Original Investigation

Abstract

Tuberculosis (TB) is a global public health problem and a source of preventable deaths each year, with 8.8 million new cases of TB and 1.6 million deaths worldwide in 2005. Approximately, 10% of infected individuals develop pulmonary or extrapulmonary TB, suggesting that host defense factors influence development of active disease. Toll-like receptor’ (TLR) polymorphisms have been associated with regulation of TLR expression and development of active TB. In the present study, 71 polymorphisms in TLR1, TLR2, TLR4, TLR6, and TLR9 were examined from 474 (295 cases and 179 controls) African-Americans, 381 (237 cases and 144 controls) Caucasians, and from 667 (321 cases and 346 controls) Africans from Guinea-Bissau for association with pulmonary TB using generalized estimating equations and logistic regression. Statistically significant associations were observed across populations at TLR9 and TLR2. The strongest evidence for association came at an insertion (I)/deletion (D) polymorphism (−196 to −174) in TLR2 that associated with TB in both Caucasians (II vs. ID&DD, OR = 0.41 [95% CI 0.24–0.68], p = 0.0007) and Africans (II vs. ID&DD, OR = 0.70 [95% CI 0.51–0.95], p = 0.023). Our findings in three independent population samples indicate that variations in TLR2 and TLR9 might play important roles in determining susceptibility to TB.

Keywords

Generalize Estimate Equation TLR9 SNPs Bandim Health Project Genotype Frequency Difference Sequenom Mass Array 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The work in this manuscript was supported by grant R01 HL068534 from the National Heart, Lung and Blood Institute. C. Hamilton acknowledges support from NIH K24-AI001833. We thank the study participants, without whom this study would have been impossible, the North Carolina TB Control Nurse Consultants (Myra Allen, Dee Foster, Julie Luffman and Elizabeth Zeringue) and county TB nurses who referred subjects to the study. We would also like to thank Martha Fletcher, Elizabeth Levine, Earline Little, and Carol Poszik for assistance in recruiting participants in South Carolina, and Courtney Linton, Regina Carney, and Ann Mosher for recruiting participants in North Carolina. The Guinea Bissau study was funded by the MRC award G0000690 to G. Sirugo, and by Grants from the Danish Medical Research Council, the Danish society of respiratory medicine, the Danish Council of Development Research to C. Wejse and R. Olesen. Integrity of research and reporting: This submitted manuscript contains experiments that comply with the current laws of the country in which they were performed.

Supplementary material

439_2009_741_MOESM1_ESM.doc (546 kb)
Supplementary material 1 (DOC 546 kb)
439_2009_741_MOESM2_ESM.doc (140 kb)
Supplementary material 2 (DOC 140 kb)

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Digna Rosa Velez
    • 1
    • 2
  • Christian Wejse
    • 9
    • 10
  • Martin E. Stryjewski
    • 5
  • Eduardo Abbate
    • 6
  • William F. Hulme
    • 1
    • 2
  • Jamie L. Myers
    • 1
    • 2
  • Rosa Estevan
    • 6
  • Sara G. Patillo
    • 4
  • Rikke Olesen
    • 9
  • Alessandra Tacconelli
    • 7
    • 8
  • Giorgio Sirugo
    • 7
    • 8
  • John R. Gilbert
    • 1
    • 2
  • Carol D. Hamilton
    • 3
    • 4
  • William K. Scott
    • 1
    • 2
    • 11
    Email author
  1. 1.Department of Human Genetics, Dr. John T. Macdonald Foundation, Miller School of MedicineUniversity of MiamiMiamiUSA
  2. 2.John P. Hussman Institute for Human Genomics, Miller School of MedicineUniversity of MiamiMiamiUSA
  3. 3.Family Health InternationalResearch Triangle ParkUSA
  4. 4.Duke University Medical CenterDurhamUSA
  5. 5.Division of Infectious Diseases, Department of MedicineCentro de Educación Médica e Investigaciones Clínicas “Norberto Quirno” (CEMIC)Buenos AiresArgentina
  6. 6.Department of MedicineHospital F.J. MuñizBuenos AiresArgentina
  7. 7.Unita’ di Genetica MedicaRomeItaly
  8. 8.Dipartimento di Biopatologia e Diagnostica per ImmaginiUniversita’ di Tor VergataRomeItaly
  9. 9.Department of Infectious DiseasesAarhus University HospitalSkejbyDenmark
  10. 10.Bandim Health ProjectDanish Epidemiology Science Centre, Statens Serum InstituteBissauGuinea-Bissau
  11. 11.MiamiUSA

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