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Investigation of chromosome 17 candidate genes in susceptibility to TB in a South African population.
Tuberculosis (Edinb). 2009 Mar; 89(2):189-94.T

Abstract

Chromosome 17 is known to contain TB susceptibility genes. Polymorphisms in two of these genes, namely NOS2A and CCL2, have been associated with TB in various populations. To investigate a possible association of gene variants with TB in the South African Coloured population we genotyped SNPs from NOS2A and CCL2 in over 800 TB cases and controls. We found a significant association between TB and two haplotypes, containing the functional rs9282799 and rs8078340 SNPs, in the NOS2A promoter. The T allele of rs8078340, found in the haplotype over-represented in cases (p=0.015, p(c)=0.038, OR=1.4, 95% CI [1.1-1.8]), was previously shown to decrease the quantity of DNA-protein complex bound as well as the duration of binding and may decrease nitric oxide (NO) production. The C allele of rs8078340 was present in the haplotype more frequent in controls (p=0.011, p(c)=0.029, OR=1.4, 95% CI [1.1-1.8]). In the single-point analysis of NOS2A, rs2779249 (previously associated with TB in Brazilians) and the functional rs8078340 were nominally associated with disease. No association was found between any of the other SNPs or haplotypes studied and TB. This study presents evidence that haplotypes in the NOS2A promoter influence susceptibility to TB and confirms the importance of NO production in the disease.

Authors+Show Affiliations

Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology and the DST/NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19147409

Citation

Möller, Marlo, et al. "Investigation of Chromosome 17 Candidate Genes in Susceptibility to TB in a South African Population." Tuberculosis (Edinburgh, Scotland), vol. 89, no. 2, 2009, pp. 189-94.
Möller M, Nebel A, Valentonyte R, et al. Investigation of chromosome 17 candidate genes in susceptibility to TB in a South African population. Tuberculosis (Edinb). 2009;89(2):189-94.
Möller, M., Nebel, A., Valentonyte, R., van Helden, P. D., Schreiber, S., & Hoal, E. G. (2009). Investigation of chromosome 17 candidate genes in susceptibility to TB in a South African population. Tuberculosis (Edinburgh, Scotland), 89(2), 189-94. https://doi.org/10.1016/j.tube.2008.10.001
Möller M, et al. Investigation of Chromosome 17 Candidate Genes in Susceptibility to TB in a South African Population. Tuberculosis (Edinb). 2009;89(2):189-94. PubMed PMID: 19147409.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigation of chromosome 17 candidate genes in susceptibility to TB in a South African population. AU - Möller,Marlo, AU - Nebel,Almut, AU - Valentonyte,Ruta, AU - van Helden,Paul D, AU - Schreiber,Stefan, AU - Hoal,Eileen G, Y1 - 2009/01/14/ PY - 2008/08/29/received PY - 2008/10/31/accepted PY - 2009/1/17/entrez PY - 2009/1/17/pubmed PY - 2010/3/6/medline SP - 189 EP - 94 JF - Tuberculosis (Edinburgh, Scotland) JO - Tuberculosis (Edinb) VL - 89 IS - 2 N2 - Chromosome 17 is known to contain TB susceptibility genes. Polymorphisms in two of these genes, namely NOS2A and CCL2, have been associated with TB in various populations. To investigate a possible association of gene variants with TB in the South African Coloured population we genotyped SNPs from NOS2A and CCL2 in over 800 TB cases and controls. We found a significant association between TB and two haplotypes, containing the functional rs9282799 and rs8078340 SNPs, in the NOS2A promoter. The T allele of rs8078340, found in the haplotype over-represented in cases (p=0.015, p(c)=0.038, OR=1.4, 95% CI [1.1-1.8]), was previously shown to decrease the quantity of DNA-protein complex bound as well as the duration of binding and may decrease nitric oxide (NO) production. The C allele of rs8078340 was present in the haplotype more frequent in controls (p=0.011, p(c)=0.029, OR=1.4, 95% CI [1.1-1.8]). In the single-point analysis of NOS2A, rs2779249 (previously associated with TB in Brazilians) and the functional rs8078340 were nominally associated with disease. No association was found between any of the other SNPs or haplotypes studied and TB. This study presents evidence that haplotypes in the NOS2A promoter influence susceptibility to TB and confirms the importance of NO production in the disease. SN - 1873-281X UR - https://www.unboundmedicine.com/medline/citation/19147409/Investigation_of_chromosome_17_candidate_genes_in_susceptibility_to_TB_in_a_South_African_population_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1472-9792(08)00121-2 DB - PRIME DP - Unbound Medicine ER -