A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians

Png, Eileen; Alisjahbana, Bachti; Sahiratmadja, Edhyana; Marzuki, Sangkot; Nelwan, R.H.H.; Balabanova, Yanina; Nikolayevskyy, Vladyslav; Drobniewski, Francis; Nejentsev, Sergey; Adnan, Iskandar; Vosse, Esther van de; Hibberd, Martin L.; Crevel, Reinout van; Ottenhoff, Tom H. M.; Seielstad, Mark

doi:10.1186/1471-2350-13-5

Cited by 91 publications

(65 citation statements)

References 39 publications

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“…Genetic variability is an important determinant of the effectiveness of the host immune response to M. tuberculosis [3]. Several lines of evidence, including twin studies [4], genome-wide linkage studies [5], and genome-wide association studies [6,7], have demonstrated that host genetic factors play a critical role in effecting the infected individuals eventually to develop TB.…”

Section: Introductionmentioning

confidence: 99%

FOXO3 rs12212067: T > G Association with Active Tuberculosis in Han Chinese Population

Zhu

Wang

et al. 2015

Inflammation

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It is well known that the human innate immune and adaptive immune response play important role in tuberculosis (TB) infection and progress. Emerging evidence shows that FOXO3 plays an important role in the human immune system. Recent research has shown that the FOXO3 genetic variants are associated malaria infection. In this study, 268 confirmed TB patients, 321 patients with latent tuberculosis infection (LTBI), and 475 TB-free controls were recruited; the single-nucleotide polymorphism (SNP) rs12212067: T > G in FOXO3 was genotyped using predesigned TaqMan® allelic discrimination assays. The results showed that the G allele of rs12212067 in FOXO3 was more common in health control and the latent TB group compared with the active TB group (p = 0.048, odds ratio (OR) 95 % confidence intervals (CI) = 1.37 (1.00-1.89); p = 0.042, OR 95 % CI = 1.42 (1.01-1.99), respectively); furthermore, within active TB patients, the G allele of rs12212067 in FOXO3 was more frequent in extra-pulmonary tuberculosis (EPTB) group compared to pulmonary tuberculosis (PTB) group (p = 0.035, OR 95 % CI = 0.57 (0.33-0.97). In conclusion, this study found that rs12212067 in FOXO3 was associated with increased risk of active TB. The minor G allele might be a protection factor which was found more common in latent TB patients and healthy controls than active TB patients.

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Section: Introductionmentioning

confidence: 99%

FOXO3 rs12212067: T > G Association with Active Tuberculosis in Han Chinese Population

Zhu

Wang

et al. 2015

Inflammation

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“…Studies of the host genetic susceptibility to TB encompass twin (3,4), linkage, candidate gene association, and genomewide association studies (5)(6)(7)(8)(9)(10)(11)(12). We and others have identified associations between common polymorphisms in innate immunity genes and susceptibility to TB and clinical phenotypes (6,8,11,13).…”

Section: Clinical Relevancementioning

confidence: 99%

Common Polymorphisms in the CD43 Gene Region Are Associated with Tuberculosis Disease and Mortality

Campo

Randhawa

Dunstan

et al. 2015

Am J Respir Cell Mol Biol

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CD43, a surface glycoprotein, regulates Mycobacterium tuberculosis macrophage binding, replication, and proinflammatory cytokine induction in a murine model. We hypothesized that single-nucleotide polymorphisms (SNPs) in the CD43 gene region are associated with human tuberculosis (TB) susceptibility. We performed a casepopulation study in discovery (352 TB cases and 382 control subjects) and validation cohorts (339 TB cases and 376 control subjects). We examined whether 11 haplotype-tagging SNPs in the CD43 gene region were associated with tuberculous meningitis (TBM) and pulmonary TB (PTB) in Vietnam. Three SNPs from the CD43 gene region were associated with TB susceptibility with a genotypic model. The association fit a recessive genetic model and was greater for TBM than for PTB (for TBM: rs4788172, odds ratio [OR], 1.64; 95% confidence interval [CI], 1.04-2.59, rs17842268 [OR, 2.20; 95% CI, 1.29-3.76, and rs12596308 [OR, 2.38; 95% CI, 1.47-3.89]). Among TBM cases, rs17842268 was associated with decreased survival (hazard ratio, 2.7; 95% CI, 1.1-6.5; P = 0.011). In addition, rs12596308 and rs17842268 were associated with focal neurologic deficit at TBM presentation. Our data suggest that CD43 polymorphisms are associated with TB susceptibility, disease manifestations, and worse outcomes. To our knowledge, this is the first report that links CD43 genetic variants with susceptibility and outcome from a disease.

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“…Host genetic factors explain, at least in part, why some people are more or less susceptible to infection. Several lines of evidence, including twin studies (48,148,242), genome-wide linkage studies (21,49,136,144,148,217), and recently published genome-wide association studies (GWAS) (135,172,229), demonstrate that host genetics strongly influences susceptibility to TB. However, assessing the contributions and functional consequences of specific genetic variations (polymorphisms) in the human genome to host susceptibility or resistance to TB remains a longstanding challenge of population genetics research, with many questions unanswered.…”

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confidence: 99%

Innate Immune Gene Polymorphisms in Tuberculosis

2012

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ABSTRACTTuberculosis (TB) is a leading cause worldwide of human mortality attributable to a single infectious agent. Recent studies targeting candidate genes and “case-control” association have revealed numerous polymorphisms implicated in host susceptibility to TB. Here, we review current progress in the understanding of causative polymorphisms in host innate immune genes associated with TB pathogenesis. We discuss genes encoding several types of proteins: macrophage receptors, such as the mannose receptor (MR, CD206), dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN, CD209), Dectin-1, Toll-like receptors (TLRs), complement receptor 3 (CR3, CD11b/CD18), nucleotide oligomerization domain 1 (NOD1) and NOD2, CD14, P2X7, and the vitamin D nuclear receptor (VDR); soluble C-type lectins, such as surfactant protein-A (SP-A), SP-D, and mannose-binding lectin (MBL); phagocyte cytokines, such as tumor necrosis factor (TNF), interleukin-1β (IL-1β), IL-6, IL-10, IL-12, and IL-18; chemokines, such as IL-8, monocyte chemoattractant protein 1 (MCP-1), RANTES, and CXCL10; and other important innate immune molecules, such as inducible nitric oxide synthase (iNOS) and solute carrier protein 11A1 (SLC11A1). Polymorphisms in these genes have been variably associated with susceptibility to TB among different populations. This apparent variability is probably accounted for by evolutionary selection pressure as a result of long-term host-pathogen interactions in certain regions or populations and, in part, by lack of proper study design and limited knowledge of molecular and functional effects of the implicated genetic variants. Finally, we discuss genomic technologies that hold promise for resolving questions regarding the evolutionary paths of the human genome, functional effects of polymorphisms, and corollary impacts of adaptation on human health, ultimately leading to novel approaches to controlling TB.

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A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians

Cited by 91 publications

References 39 publications

FOXO3 rs12212067: T > G Association with Active Tuberculosis in Han Chinese Population

FOXO3 rs12212067: T > G Association with Active Tuberculosis in Han Chinese Population

Common Polymorphisms in the CD43 Gene Region Are Associated with Tuberculosis Disease and Mortality

Innate Immune Gene Polymorphisms in Tuberculosis

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