Interferon‐γ Receptor‐1 Gene Polymorphism in Tuberculosis Patients from Croatia

Fraser, DA; Bulat-Kardum, Ljiljana; Knežević, Jelena; Babarovic, P.; Mataković-Mileusnić, Nataša; Dellacasagrande, Jérôme; Matanić, Dubravka; Pavelić, Jasminka; Beg-Zec, Zlata; Dembić, Zlatko

doi:10.1046/j.1365-3083.2003.01253.x

Cited by 49 publications

(60 citation statements)

References 28 publications

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“…We therefore cannot exclude a causal variant elsewhere in the gene. A weak association between the intron 6 IFNGR1 microsatellite and pulmonary TB has been reported in a Croatian population, 20 but we did not replicate this finding in this Gambian sample. 21 Secondly, we have investigated pulmonary TB which is caused by reactivation of latent infection.…”

Section: Discussioncontrasting

confidence: 55%

No association between interferon- receptor-1 gene polymorphism and pulmonary tuberculosis in a Gambian population sample

Awomoyi

Nejentsev²,

Richardson³

et al. 2004

Thorax

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Background: Tuberculosis (TB) is a major global cause of mortality and morbidity, and host genetic factors influence disease susceptibility. Interferon-c mediates immunity to mycobacteria and rare mutations in the interferon-c receptor-1 gene (IFNGR1) result in increased susceptibility to mycobacterial infection, including TB, in affected families. The role of genetic variation in IFNGR1 in susceptibility to common mycobacterial diseases such as pulmonary TB in outbred populations has not previously been investigated. Methods: The association between IFNGR1 and susceptibility to pulmonary TB was investigated in a Gambian adult population sample using a case-control study design. The coding and promoter regions of IFNGR1 were sequenced in 32 patients with pulmonary TB, and the frequencies of six common IFNGR1 polymorphisms were determined using PCR based methods in 320 smear positive TB cases and 320 matched controls. Haplotypes were estimated from the genotype data using the expectation-maximisation algorithm.Results: There was no association between the IFNGR1 variants studied and TB in this Gambian population sample. Three common haplotypes were identified within the study population, none of which was associated with TB. Conclusions: These data represent an important negative finding and suggest that, while IFNGR1 is implicated in rare Mendelian susceptibility to mycobacterial disease, the common variants studied here do not have a major influence on susceptibility to pulmonary TB in The Gambian population. and signal transducer and activator of transcription-1 (MIM #600555) 9 also result in increased susceptibility to mycobacterial infection. Several other IFNGR1 mutations have since been identified in patients with MSMI, the majority of which result either in complete absence of surface expression of the protein or expression of an abnormal protein that does not bind IFN-c signalling is completely abrogated and the clinical phenotype correspondingly severe, often resulting in death from disseminated infection at an early age. Other mutations, however, lead to the expression of a dysfunctional protein and impairment-but not complete abrogation-of IFN-c signalling. In this partial form of IFN-c receptor-1 deficiency the phenotype is less severe and patients respond to IFN-c treatment.10 Infection with virulent M tuberculosis has been reported in partial IFN-c receptor-1 deficiency. 11These observations suggest a spectrum in which disease severity correlates with the degree of functional impairment in the IFN-c receptor.Host genetic factors have an important role in the development of clinical disease following infection with M tuberculosis, but inheritance of TB susceptibility in the general population is non-Mendelian. The correlation between the molecular pathology, mycobacterial virulence, and clinical phenotype in inherited IFN-c receptor-1 deficiency suggests that more subtle variation in IFNGR1 could contribute to M tuberculosis disease susceptibility in an outbred population. To test this hypothesis, ...

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Section: Discussioncontrasting

confidence: 55%

No association between interferon- receptor-1 gene polymorphism and pulmonary tuberculosis in a Gambian population sample

Awomoyi

Nejentsev²,

Richardson³

et al. 2004

Thorax

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“…In the present study, PIC value is 0.785 among the controls for the CA repeat site. This result is in accordance with data from other different populations (0.82 from Croatia [21], 0.90 or so on the basis of the heterozygosity degree in two consanguineous kindreds from Malta and Tunisia [22] and 0.80 from Gambian [23]). All the data indicated that the marker locus is relatively highly informative and the CA repeat may be a good marker for association studies?…”

Section: Discussionsupporting

confidence: 92%

“…One allele with the highest frequency should be primordial and the other alleles at the same locus were originated from the allele with the highest frequency. According to this principle, (CA) 13 is primordial in the Chinese and Croatia populations and, in the Gambia population, (CA) 21 is primordial (Fig. 1).…”

Section: Discussionmentioning

confidence: 99%

Interferon Gamma Receptor 1 Gene Polymorphism in Patients with Tuberculosis in China

Ding

Wang

et al. 2008

Scand J Immunol

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The aim of the study was to examine the influence of the CA microsatellite polymorphisms of interferon gamma receptor 1 on patients with tuberculosis (TB) in the south‐eastern Chinese population. Genomic DNA from patients with TB (n = 155) and ethnically matched controls (n = 89) were genotyped by short tandem repeat‐PCR method. The allele frequency of (CA)25 was 1.70‐fold higher among patients than that among controls (95% CI 1.07–2.70) (P = 0.025). Compared with the non‐(CA)25/non‐(CA)25 reference group, the risk to TB of the carriers of (CA)25/(CA)25 genotypes were 6.46‐fold (95% CI 1.40–29.74) (P = 0.0017) higher. On the contrary, the allele frequency of (CA)26 was 0.29‐fold lower in patients than that in controls (95% CI 0.11–0.76) (P = 0.012). Genotypes with (CA)26 allele were at 0.35‐fold (95% CI 0.13–0.98) (P = 0.045) lower to the risk of TB, compared with that of the non‐(CA)26/non‐(CA)26 in the reference group. The above results indicated that the allele (CA)25 appeared to be susceptible to TB, while the allele (CA)26 to be protective towards TB. Our data also suggest that the CA repeat was a highly polymorphic marker and could be used for linkage and association analysis.

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“…Allele frequency analysis was conducted on blood samples of 810 healthy donors (Department of Transfusion Medicine, Zagreb and Rijeka, Croatia) and 210 tuberculosis patients (Department of Internal Medicine, Section of Pulmonology, Clinical Hospital Center, University of Rijeka, Rijeka, Croatia) as described (19,20). All study subjects provided oral and written informed consent.…”

Section: Methodsmentioning

confidence: 99%

Heterozygous Carriage of a Dysfunctional Toll-like Receptor 9 Allele Affects CpG Oligonucleotide Responses in B Cells

Knežević

Pavlinić

Rose

et al. 2012

Journal of Biological Chemistry

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Background: Human B cells respond to Toll-like receptor (TLR) 9 stimulation by cytokine production. Results: A rare, novel TLR9 allele fails to activate NF-B in HEK293 cells. Heterozygous carrier B cells show defective IL-6 and IL-10 production. Conclusion: Heterozygosity for this TLR9 allele modifies CpG oligonucleotide responsiveness. Significance: This is the first analysis of human TLR9 variants in primary cells.

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Interferon‐γ Receptor‐1 Gene Polymorphism in Tuberculosis Patients from Croatia

Cited by 49 publications

References 28 publications

No association between interferon- receptor-1 gene polymorphism and pulmonary tuberculosis in a Gambian population sample

No association between interferon- receptor-1 gene polymorphism and pulmonary tuberculosis in a Gambian population sample

Interferon Gamma Receptor 1 Gene Polymorphism in Patients with Tuberculosis in China

Heterozygous Carriage of a Dysfunctional Toll-like Receptor 9 Allele Affects CpG Oligonucleotide Responses in B Cells

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