The IFNG rs1861494 Single Nucleotide Polymorphism Is Associated with Protection against Tuberculosis Disease in Argentina

Rolandelli, Agustín; Pellegrini, Joaquín Miguel; Amiano, Nicolás Oscar; Santilli, Maria Cecilia; Morelli, María Paula; Castello, Florencia Andrea; Tateosian, Nancy Liliana; Levi, Alberto; Casco, Nicolás; Palmero, Domingo; García, Verónica

doi:10.3390/genes9010046

Cited by 14 publications

(8 citation statements)

References 47 publications

(53 reference statements)

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“…The initial immunofluorescence identification of islet cell antibodies (ICA) in 1974 [66, 67] was a key step in recognizing type 1 diabetes as an immune-mediated disease. The ICA can identify any antibody that binds to human islet tissues in a nonspecific manner with immunofluorescent techniques [66, 67]. However, the ICA assay is difficult to standardize because it is operator-dependent, varies according to the quality of the human pancreatic tissue used as a substrate, and recognizes heterogeneous antibodies that vary among individuals.…”

Section: Introductionmentioning

confidence: 99%

Human Leukocyte Antigen (HLA) and Islet Autoantibodies Are Tools to Characterize Type 1 Diabetes in Arab Countries: Emphasis on Kuwait

Jahromi

Al-Ozairi

2019

Disease Markers

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The incidence rate of type 1 diabetes in Kuwait had been increasing exponentially and has doubled in children ≤ 14 years old within almost two decades. Therefore, there is a dire need for a careful systematic familial cohort study. Several immunogenetic factors affect the pathogenesis of the disease. The human leukocyte antigen (HLA) accounts for the major genetic susceptibility to the disease. The triggering agents initiate disease onset by type 1 destruction of pancreatic β-cells. Both HLA and anti-islet antibodies can be used to characterize, predict susceptibility to the disease, innovate, or delay the β-cell destruction. Evidence from prospective longitudinal studies suggested that the underlying disease process represents a continuum that begins before the symptoms are clinically evident. Autoimmunity of the functional pancreatic β-cells results in symptomatic type 1 diabetes and lifelong insulin dependence. The autoantibodies against glutamic acid decarboxylase (GADA), insulinoma antigen-2 (IA-2A), insulin (IAA), and zinc transporter-8 (ZnT-8A) comprise the most reliable biomarkers for type 1 diabetes in both children and adults. Although Kuwait is the second among the top 10 countries with a high incidence rate of type 1 diabetes, there have been no proper diagnostic and prediction tools as per the World Health Organization. The Kuwaiti Type 1 Diabetes Study (KADS) was initiated to understand the disease pathogenesis as well as the HLA and anti-islet autoantibody profile of type 1 diabetes in Kuwait. Understanding the disease sequela in a homogenous gene pool and highly consanguineous population of Kuwaitis could help solve the challenges and pathogenesis, as well as hasten the prevention, of type 1 diabetes.

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Section: Introductionmentioning

confidence: 99%

Human Leukocyte Antigen (HLA) and Islet Autoantibodies Are Tools to Characterize Type 1 Diabetes in Arab Countries: Emphasis on Kuwait

Jahromi

Al-Ozairi

2019

Disease Markers

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“…Several studies have been conducted to investigate the association between rs1861494 polymorphism and tuberculosis, but the results were inconsistent. A study from Argentina showed that rs1861494 polymorphism was associated with tuberculosis resistance in a dominant model [34]. Also, another study demonstrated that GG genotype was related to tuberculosis [35].…”

Section: Discussionmentioning

confidence: 99%

Genetic Polymorphisms ofIFNGandIFNGR1with Latent Tuberculosis Infection

Liu

Wang

et al. 2019

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Previous studies indicated that single-nucleotide polymorphisms (SNPs) of interferon gamma (IFNG) and IFNG receptor 1 (IFNGR1) may be involved in the pathogenesis of pulmonary tuberculosis (PTB) in different populations. In order to further explore the results in a Chinese Han population, this study was designed to investigate potential associations between the polymorphisms in IFNG and IFNGR1 and susceptibility to latent tuberculosis infection (LTBI) and/or PTB in a Chinese Han population. A total of 209 PTB, 173 LTBI, and 183 healthy control subjects (HCS) were enrolled in our study. Genotyping was conducted using an improved multiplex ligase detection reaction (iMLDR). We performed a logistic regression including sex and age as covariates to test the effect of alleles/genotypes on LTBI and/or TB. All six markers studied in IFNG and IFNGR1 conformed to the Hardy–Weinberg equilibrium (HWE). The IFNG rs1861494 was significantly associated with LTBI in recessive model, and the CC+CT genotype decreased risk of LTBI by 50% (P = 0.046, OR = 0.50, 95%CI: 0.25-0.99). The IFNGR1 rs2234711 was significantly associated with LTBI, and allele A increased the risk of LTBI by 55% (P = 0.047, OR = 1.55, 95%CI: 1.00-2.40). In the present study, we found that IFNG and IFNGR1 polymorphisms were associated with LTBI.

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“…Consequently, patients with tuberculosis (TB) displaying the most severe expression of the disease produce the lowest amounts of IFNG against the pathogen (5, 6). Moreover, we have reported that the IFNG rs1861494 single nucleotide polymorphism (SNP) would act as a biomarker of resistance to tuberculosis in the Argentinean population, since it affects the secretion of IFNG (7). However, other cytokines might be participating in the fight of the host against Mtb infection, given that only IFNG is not enough to completely eliminate the bacteria (8).…”

Section: Introductionmentioning

confidence: 99%

The Non-synonymous rs763780 Single-Nucleotide Polymorphism in IL17F Gene Is Associated With Susceptibility to Tuberculosis and Advanced Disease Severity in Argentina

et al. 2019

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Th17 lymphocytes, that produce IL17A, IL17F, and IL22, play a crucial role during the immune response against Mycobacterium tuberculosis (Mtb) infection. Whereas, the contribution of IL17A in immunity to tuberculosis is usually accepted, the role of IL17F has been scarcely studied so far. The aim of this work was to evaluate the existence of a potential association of the non-synonymous variant rs763780 SNP of the IL17F gene with human tuberculosis. Accordingly, by comparing healthy donors (HD) and tuberculosis patients (TB) populations we demonstrated an association between the C allele of the SNP and the susceptibility to tuberculosis disease in Argentina. Furthermore, we found that peripheral blood mononuclear cells (PBMCs) from individuals with a more effective immune response against Mtb secreted the highest levels of IL17F when stimulated with a lysate of Mtb (Mtb-Ag). Besides, we evidenced that Mtb-Ag-stimulated PBMCs from HD carrying the C variant of the SNP displayed the lowest IFNG secretion, proliferation index, and SLAM expression as compared to TT carriers. Moreover, Mtb-Ag-stimulated PBMCs from TB carrying the C allele produced the lowest levels of IFNG, the highest level of IL17A, and the minimum proliferation indexes as compared to TT TB, suggesting a relationship between the C allele and tuberculosis severity. In fact, TB carrying the C allele presented a more severe disease, with the highest bacilli burden in sputum. Together, our findings identify the IL17F rs763780 SNP as a biomarker of tuberculosis susceptibility and advanced disease severity in Argentina, suggesting that IL17F could be a critical cytokine in tuberculosis immunity.

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The IFNG rs1861494 Single Nucleotide Polymorphism Is Associated with Protection against Tuberculosis Disease in Argentina

Cited by 14 publications

References 47 publications

Human Leukocyte Antigen (HLA) and Islet Autoantibodies Are Tools to Characterize Type 1 Diabetes in Arab Countries: Emphasis on Kuwait

Human Leukocyte Antigen (HLA) and Islet Autoantibodies Are Tools to Characterize Type 1 Diabetes in Arab Countries: Emphasis on Kuwait

Genetic Polymorphisms ofIFNGandIFNGR1with Latent Tuberculosis Infection

The Non-synonymous rs763780 Single-Nucleotide Polymorphism in IL17F Gene Is Associated With Susceptibility to Tuberculosis and Advanced Disease Severity in Argentina

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