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NOS2A, TLR4, and IFNGR1 interactions influence pulmonary tuberculosis susceptibility in African-Americans.

Publication ,  Journal Article
Velez, DR; Hulme, WF; Myers, JL; Weinberg, JB; Levesque, MC; Stryjewski, ME; Abbate, E; Estevan, R; Patillo, SG; Gilbert, JR; Hamilton, CD; Scott, WK
Published in: Hum Genet
November 2009

Tuberculosis (TB) has substantial mortality worldwide with 5-10% of those exposed progressing to active TB disease. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS) molecule plays an important role in immune response to TB. A mixed case-control association study of individuals with TB, relatives, or close contact controls was performed in 726 individuals (279 case and 166 control African-Americans; 198 case and 123 control Caucasians). Thirty-nine single nucleotide polymorphisms (SNPs) were selected from the NOS2A gene for single SNP, haplotype, and multilocus interaction analyses with other typed candidate genes using generalized estimating equations. In African-Americans, ten NOS2A SNPs were associated with TB. The strongest associations were observed at rs2274894 (odds ratio (OR) = 1.84, 95% confidence interval (CI) [1.23-2.77], p = 0.003) and rs7215373 (OR = 1.67, 95% CI [1.17-2.37], p = 0.004), both of which passed a false discovery rate correction for multiple comparisons (q* = 0.20). The strongest gene-gene interactions were observed between NOS2A rs2248814 and IFNGR1 rs1327474 (p = 0.0004) and NOS2A rs944722 and IFNGR1 rs1327474 (p = 0.0006). Three other SNPs in NOS2A interacted with TLR4 rs5030729 and five other NOS2A SNPs interacted with IFNGR1 rs1327474. No significant associations were observed in Caucasians. These results suggest that NOS2A variants may contribute to TB susceptibility, particularly in individuals of African descent, and may act synergistically with SNPs in TLR4 and IFNGR1.

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Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

November 2009

Volume

126

Issue

5

Start / End Page

643 / 653

Location

Germany

Related Subject Headings

  • White People
  • United States
  • Tuberculosis, Pulmonary
  • Toll-Like Receptor 4
  • Receptors, Interferon
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Nitric Oxide Synthase Type II
  • Models, Genetic
  • Male
 

Citation

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Velez, D. R., Hulme, W. F., Myers, J. L., Weinberg, J. B., Levesque, M. C., Stryjewski, M. E., … Scott, W. K. (2009). NOS2A, TLR4, and IFNGR1 interactions influence pulmonary tuberculosis susceptibility in African-Americans. Hum Genet, 126(5), 643–653. https://doi.org/10.1007/s00439-009-0713-y
Velez, Digna Rosa, William F. Hulme, Jamie L. Myers, J Brice Weinberg, Marc C. Levesque, Martin E. Stryjewski, Eduardo Abbate, et al. “NOS2A, TLR4, and IFNGR1 interactions influence pulmonary tuberculosis susceptibility in African-Americans.Hum Genet 126, no. 5 (November 2009): 643–53. https://doi.org/10.1007/s00439-009-0713-y.
Velez DR, Hulme WF, Myers JL, Weinberg JB, Levesque MC, Stryjewski ME, et al. NOS2A, TLR4, and IFNGR1 interactions influence pulmonary tuberculosis susceptibility in African-Americans. Hum Genet. 2009 Nov;126(5):643–53.
Velez, Digna Rosa, et al. “NOS2A, TLR4, and IFNGR1 interactions influence pulmonary tuberculosis susceptibility in African-Americans.Hum Genet, vol. 126, no. 5, Nov. 2009, pp. 643–53. Pubmed, doi:10.1007/s00439-009-0713-y.
Velez DR, Hulme WF, Myers JL, Weinberg JB, Levesque MC, Stryjewski ME, Abbate E, Estevan R, Patillo SG, Gilbert JR, Hamilton CD, Scott WK. NOS2A, TLR4, and IFNGR1 interactions influence pulmonary tuberculosis susceptibility in African-Americans. Hum Genet. 2009 Nov;126(5):643–653.
Journal cover image

Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

November 2009

Volume

126

Issue

5

Start / End Page

643 / 653

Location

Germany

Related Subject Headings

  • White People
  • United States
  • Tuberculosis, Pulmonary
  • Toll-Like Receptor 4
  • Receptors, Interferon
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Nitric Oxide Synthase Type II
  • Models, Genetic
  • Male