IFN-γ Gene Polymorphisms Research Articles

Association between interferon-gamma (IFN-γ) gene polymorphisms and tuberculosis susceptibility: a systematic review and meta-analysis

Interferon-gamma (IFN-γ) has been established to play a pivotal role in the pathogenesis of tuberculosis (TB). Existing evidence suggests a potential association between the genetic poly­morphisms of IFN-γ and the susceptibility to TB. However, this association remains a topic of controversy. To address this knowledge gap, a meta-analysis was conducted to provide more accurate results regarding their relationship. The pooled odds ratio along with its corresponding 95% confidence interval was calculated using four different gene models. This analytical approach served to evaluate the strength of the association between single nucleotide polymorphisms (SNPs) and TB susceptibility. Additionally, we determined whether a fixed effect model or a random effect model should be applied based on the extent of heterogeneity. Egger’s test was used to evaluate publication bias. This study included a total of nine studies, involving 4509 patients with TB and 4378 healthy controls. In non-Asian populations, a C > T mutation at polymorphic variant rs2069705 and a T > C mutation at rs2069718 was associated with an increased risk of TB. Conversely, among Asians, the variants rs2069705, rs2069718, and rs1861494 were not significantly associated with the risk of TB. Importantly, our investigation did not reveal any significant publication bias in the pooled results of the four gene models. In conclusion, this meta-analysis suggests that two SNPs in IFN-γ may be associated with TB susceptibility in non-Asian populations. However, for Asians, there is no evidence to support a conclusive relationship between these SNPs and the risk of TB.

IFN-gene polymorphisms as a risk factor for tuberculosis infection in Asian populations: A meta-analysis.

The purpose of this meta-analysis is to verify that rs1861494 and rs2069718, two polymorphisms in the IFN-gene, are associated with tuberculosis (TB) infection in Asian populations. To find appropriate case-control studies, a search was done from the databases, including Google Scholar, Science Direct, Embase, and PubMed. With the aid of MetaGenyo software, statistical analyses were performed. Case and control studies from the available database were used to investigate the relationship between IFN-γ gene polymorphisms and TB infection risk. The protocol for the present meta-analysis was registered using PROSPERO (ID Number: 443605). Information obtained through examining two different variants of the IFN-γ gene showed associations with recessive, allelic, overdominant, and dominant models. This indicates that the statistical value obtained was found to be statistically significant at P = 0.05. The findings of the IFN-γ rs1861494 gene polymorphisms for allelic, dominant, and overdominant models were statistically significant with P > 0.05, whereas the recessive model exhibited a statistically insignificant value (P = 0.25). The IFN-γ rs2069718 gene polymorphism demonstrated statistically significant value for overdominant, recessive, and allelic models (P > 0.05). However, the dominant model shows a statistically insignificant value P = 0.11. The two genetic variations of the IFN-γ gene polymorphisms (rs1861494 and rs2069718) and their association with TB were confirmed by the meta-analysis conducted. More in-depth research into the molecular basis of the association is necessary, and larger-scale epidemiological studies are needed to confirm these findings.

Relationship between IL-17, TNF-α, IL-10, IFN-γ, and IL-18 polymorphisms with the outcome of hepatitis B virus infection in the Turkish population.

Hepatitis B virus is a global threat that can lead to liver cirrhosis and hepatocellular carcinoma. For the treatment of chronic hepatitis B virus, polymorphisms might be an option for gene treatments. This study aimed to investigate the effects of IL-17, TNF-α, IL-10, IFN-γ, and IL-18 gene polymorphisms on hepatitis B virus infection in the Turkish population. The genotypes and allele distribution of 75 patients exposed to hepatitis B virus and 50 healthy control individuals were analyzed. The real-time polymerase chain reaction method was used for identification. A correlation was observed between susceptibility to hepatitis B virus infection and IL-17 Exon 3/3'UTR (rs1974226) C, IL-17 Exon 3 (rs763780) A, IL-18 (-607) (rs1946518) A alleles, and IL-17 Exon 3 (rs763780) AA genotype (p=0.006, p=0.009, p=0.025, and p=0.008, respectively). Furthermore, IL-18 (-137) (rs187238) TT genotype and TNF-α-308 (rs1800629) G and A alleles, were associated with protection against hepatitis B virus infection (p=0.0351 and p=0.032, respectively). This study demonstrated that TNF-α (-308), IL-17 (Exon 3/3' UTR), IL-17 (Exon 3), and IL-18 (-607) polymorphisms are associated with hepatitis B virus infection. Therefore, these may serve as potential therapeutic targets for chronic viral hepatitis in the Turkish population.

Lack of Association between IFN-γ, CXCL10 and TGF-β1 Gene Polymorphisms and Liver Complication in HIV-infected Thais.

Objective:Chronic liver disease has become a leading cause of illness and death in people living with HIV and the production of the cytokines IFN-γ and TGF-β1, and chemokine CXCL10 during chronic inflammation contributes to liver disease progression in HIV patients under long-term anti-retroviral therapy. This study aimed to examine association of IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-β1 -509C/T single nucleotide polymorphisms (SNPs) with liver complications in the HIV-infected Thais. Methods:A cross-sectional study was conducted in 200 Thai HIV patients who were evaluated for transaminitis and significant liver fibrosis by fibrosis-4 score (FIB-4), and genotypes for IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-β1 -509C/T SNPs using PCR-based methods. Result:There were high rates of transaminitis (30.1%) and significant liver fibrosis assessed by FIB-4 score > 1.45 (18.8%) in this group of patients, mostly under anti-retroviral therapy (73.0%). The genotypes and alleles of IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-β1 -509C/T SNPs were not associated with either transaminitis or FIB-4 score > 1.45 (p > 005). Logistic regression analysis identified age and gender as risk factors, and CD4+ cell count higher than 350 cells/ul as a protective factor of liver fibrosis in this study group.Conclusion:The IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-β11 -509C/T SNPs were not significantly associated with liver complication in HIV-infected Thais, mostly under ART.

Association between interferon-gamma (IFN-γ) gene polymorphisms (+874A/T and +2109A/G), and susceptibility to hepatitis B viral infection (HBV)

Interferon-gamma (IFN-γ) is a chief proinflammatory cytokine with a significant role in the immune response against viral infections. Today there is increasing evidence about the association between individual genetic polymorphisms and cytokines in predicting HBV infection susceptibility. This study aimed to investigate the association between IFN-γ gene polymorphisms and susceptibility to hepatitis B viral infection (HBV), and the impact of these genetic polymorphisms on IFN-γ production. IFN-γ (+874A/T, rs2430561, and +2109A/G, rs1861494) was genotyped by single-stranded polymorphism-polymerase chain reaction (SSP-PCR) in 126 Egyptians with chronic HBV infection and in 100 healthy control subjects. The plasma levels of IFN-γ were measured by Enzyme-linked immunosorbent assay (ELISA). Compared to the control subjects there was a slight increase in +874TT genotype frequency in HBV patients. However, no statistical significance in IFN-γ (+874A/T and +2109A/G) genotype/allele distribution was demonstrated, indicating the lack of association between these SNPs and susceptibility to HBV infection. In +2109A/G, only AG genotype was observed with a complete abrogation of GG and AA genotypes. Haplotypes between different loci on selected genes showed insignificant changes in their frequency in patients and control subjects. HBV patients had a significantly higher level of IFN-γ (P < 0.001) compared to controls. The maximum significant increase in IFN-γ production was observed in subjects harboring the +874TA genotype. As no association could be characterized between the polymorphism in IFN-γ (+874A/T and +2109A/G) and susceptibility to chronic HBV infection, our data support the concept that IFN-γ gene polymorphisms are not predictors of HBV susceptibility in this segment of the Egyptian population.

Ethnicity based comprehensive evaluation of polymorphism in interferon-gamma gene and its association with pulmonary and extra-pulmonary tuberculosis risk: An updated trial sequential meta-analysis.

Host genetic background plays an important role in susceptibility to intracellular infectious pathogens like Mycobacterium tuberculosis (Mtb). Cellular immune response activation is vital for protection to these pathogens. Interferon-gamma (IFN-γ) plays a crucial role in this activation and preventing the intracellular growth of Mtb. A mutation in the IFN-γ gene, therefore, may lead to increased susceptibility to tuberculosis (TB) that may vary in different ethnic groups and its consequence also varies in pulmonary and extra-pulmonary TB (EPTB). Several IFN-γ gene polymorphisms are investigated for susceptibility to TB, but their associations are not always consistent as its impact may vary from one ethnicity to the other as well as with the type of TB. Hence, we performed a meta-analysis to overcome this problem. The present study involves comprehensive meta-analysis of + 874T/A polymorphism in the IFN-γ gene based on type of TB within five different ethnic groups to show its association with increased susceptibility to TB. Using PubMed and Google Scholar databases, a total of 50 case-control studies were retrieved having 8152 cases and 9755 controls in this meta-analysis. Thirty-eight studies of + 874T/A polymorphism of IFN-γ gene were correlated for Pooled odds ratios with 95% confidence intervals. The polymorphism was analyzed for six genetic models for five major ethnic groups accounting for heterogeneity among studies. Moreover, the sub-group analysis was based on the type of TB within each ethnic group. Trial sequential analysis was also performed for all the sub-groups to estimate the statistical consistency. IFN-γ +874 T/A polymorphism analysis clearly confirmed the increased association of + 874AA genotype with increased TB risk. This polymorphism also showed significant association in East Asian, European, American, and African ethnic groups whereas no such association was found in Asians. Patients with pulmonary TB (PTB) confirmed the association in East Asians, Africans, and Americans, whereas patients with EPTB showed association in Asian and East Asian populations only. This study reaffirms the association of IFN-γ+874 T/A polymorphism with TB risk. It specifically confirms that IFN-γ+874 T/A polymorphism increases the susceptibility of pulmonary infection in Africans and Americans, while the East Asian population is more susceptible to both, pulmonary and EPTB.

Predictive Value of Interferon γ Receptor Gene Polymorphisms for Hepatocellular Carcinoma Susceptibility.

Background:Recent reports suggested relation between Interferon Gamma (IFN-γ) gene polymorphism and the risk of development of HCC on top of hepatic cirrhosis. The aim of this study was to address the predictive value of Interferon Gamma gene receptor (IFN-γR) polymorphisms for the occurrence of hepatocellular carcinoma on top of liver cirrhosis. Patients and Methods:This is a case control study performed on patients selected from the outpatient hepatology clinic, specialized medical hospital, Mansoura University, Egypt, from August 2017 to February 2019. The included patients were categorized into two groups; 60 patients with HCC on top of cirrhosis and 20 patients with hepatic cirrhosis. For all patients IFN-γR polymorphism was identified by RFLP. Results:Our study showed that HCC patients had male predominance. Additionally, diabetes mellitus (DM) was found in 28.3% of total HCC patients. Half of HCC patients in this study were from rural areas (50%). The frequency of AA at position -611 in the IFN-γR (-611 IFN-γR) was significantly higher in the HCC group as compared to cirrhotic group (P=0.021). Moreover; the frequency of CC and CT genotypes of IFN-γR -56 was not significantly different in HCC group as compared to control group (P>0.05). The IFN-γR (-611 IFN-γ) AA genotype significantly increased risk of HCC (OR= 0.78, 95% CI= 0.10-6.39; P= 0.042).Conclusion:The analysis of IFN-γR -611 single nucleotide gene polymorphism could be a valuable marker for predicting subgroup of cirrhotic patients with high risk of developing HCC. Cirrhotic patients have AA genotype of IFN-γR-611 recommended to be under close follow up.

The Impact of Interferon-γ (IFN-γ) and IFN-γ-Inducible Protein 10 (IP-10) Genes’ Polymorphism on Risk of Hepatitis C Virus–Related Liver Cirrhosis

ABSTRACT Background Today there is increasing evidence concerning the association between individual genetic polymorphisms within proinflammatory cytokines and chronic hepatitis C (CHC) severity. It has been demonstrated that polymorphisms in some genes may significantly predict HCV infected patients’ susceptibility to developing liver cirrhosis or their responsiveness to the treatment. Aim We investigated the influence of single nucleotide polymorphisms (SNPs) in Interferon (IFN-γ) and Interferon Gamma-Inducible Protein 10 (IP-10) genes on cirrhosis risk in HCV-infected patients and their association with response to various direct-acting antiviral drugs (DAAs). Methods IFN-γ (+874T/A, +2109A/G) and IP-10 (−135G/A, −1447A/G) genotypes were determined in 175 CHC Egyptian HCV patients (69 liver cirrhotic and 106 non-cirrhotic patients) using either single-stranded polymorphism polymerase chain reaction (SSP-PCR) or Restriction fragment length-PCR (RFLP-PCR) methods. Results IFN-γ + 874 TA, IP-10 − 135AA, and IP-10 − 1447AA and IP-10 − 1447GG genotypes are increased in patients developing liver cirrhosis compared to non-cirrhotic ones. Although, no statistical significance in their distribution was demonstrated, indicating the lack of association between these SNPs and liver cirrhosis susceptibility in HCV-infected patients. Haplotypes analysis between different loci on all selected genes showed a significant increase in AGGA and TAGA and a significant decrease in TGGA haplotypes in cirrhotic patients. Genotype frequencies at loci −135 and −1447 of IP-10 appeared to be in complete Linkage disequilibrium (LD) (D’ = 0.999, r2 = 0.689). Conclusion Our data support the concept that IFN-γ and IP-10 gene polymorphisms are not predictors of disease progression among Egyptian patients with HCV infection.

INF-γ Plasma Level and Polymorphism Significance in Autastic Spectrum Disorder, A Controlled Study in Basrah

ASD are particularly heterogeneous developmental conditions. Many arguments clarified a central function for dysregulation of immune system in ASD and many ASD hazard genes encode the immune system elements along with other risk factors. There is also evidence of continuing dysregulation of immune system in people with ASD and in animal models of this condition. Objectives: This study was performed to investigate the relationship between the IFN-γ + 874 gene polymorphism and INF - γ plasma level with susceptibility to ASD Methods: Polymorphism detection analysis was performed on 194 subjects from Basra south Iraq. 94 patients with ASD, (78 (83%) males and 16 (17%) females), their age ranging from 2 to 13 years, and 100 children apparently healthy control group matching for the same age and sex The IFN-γ gene polymorphism (+874A/T) was genotyped through a specific sequence primer polymerase chain reaction (SSP-PCR). For all participant the plasma level of INF-γ was determined by ELISA KIT (Elabscience, USA, Catalog No: E-EL-H0108), followed the manufacturer instructions Results: showed sufficient differences in the plasma concentration of INF between children with autism and the none group: 24.87 pg/mm2 18.86 pg/ mm respectively, with significant increase in plasma concentration of IFN of male and female of autistic group as compare to control group. Results of iterative distribution of INF-γ+874 gene polymorphism showed heterogeneous results between autistic group and control group, as the T allele was scored in autistic group 23.4% in compared with A allele which scored 79.7%, while in control group the T allele was scored 67% in compared with A allele which was scored 85%. AA genotypes of IFN-γ+874 showed higher recurrence among autistic group in compared to control group,(76.5% vs 33% respectively), while TA genotypes of IFN-γ+874 showed lower recurrence in autistic group when compared to control group,(3.2% vs 52% respectively),and IFN-γ+874 TT genotypes scored 20.2% in autistic patients and 15% was scored in control group ASD susceptibility is associated with the T allele of +874 rs2430561 with increase plasma level of IFN-γ which may have role in the severity of behavioural changes.

Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children.

Background: Anaemia is a major public health concern especially in African children living in malaria-endemic regions. Interferon-gamma (IFN-γ) is elevated during malaria infection and is thought to influence erythropoiesis and iron status. Genetic variants in the IFN-γ gene (IFNG) are associated with increased IFN-γ production. We investigated putative functional single nucleotide polymorphisms (SNPs) and haplotypes of IFNG in relation to nutritional iron status and anaemia in Gambian children over a malaria season. Methods: We used previously available data from Gambian family trios to determine informative SNPs and then used the Agena Bioscience MassArray platform to type five SNPs from the IFNG gene in a cohort of 780 Gambian children aged 2-6 years. We also measured haemoglobin and biomarkers of iron status and inflammation at the start and end of a malaria season. Results: We identified five IFNG haplotype-tagging SNPs ( IFNG-1616 [rs2069705], IFNG+874 [rs2430561], IFNG+2200 [rs1861493], IFNG+3234 [rs2069718] and IFNG+5612 [rs2069728]). The IFNG+2200C [rs1861493] allele was associated with reduced haemoglobin concentrations (adjusted β -0.44 [95% CI -0.75, -0.12]; Bonferroni adjusted P = 0.03) and a trend towards iron deficiency compared to wild-type at the end of the malaria season in multivariable models adjusted for potential confounders. A haplotype uniquely identified by IFNG+2200C was similarly associated with reduced haemoglobin levels and trends towards iron deficiency, anaemia and iron deficiency anaemia at the end of the malaria season in models adjusted for age, sex, village, inflammation and malaria parasitaemia. Conclusion: We found limited statistical evidence linking IFNG polymorphisms with a risk of developing iron deficiency and anaemia in Gambian children. More definitive studies are needed to investigate the effects of genetically influenced IFN-γ levels on the risk of iron deficiency and anaemia in children living in malaria-endemic areas.

Study of TNF-α, IFN-γ, TGF-β, IL-6, and IL-10 gene polymorphism in individuals from the leprosy endemic area in the Brazilian Amazon

This study aimed to verify the relationship between the polymorphisms of the cytokines TNF-α rs1800629; IFN-γ rs2430561; TGF-β rs1982073 e rs1800471; IL-6 rs180079 e IL-10 rs1800896, rs1800871 and rs1800872 and leprosy. Blood samples were analyzed from 106 individuals, of whom 24 were paucibacillary (PB), 28 were multibacillary (MB), 32 intradomiciliary consanguineal contacts of patients (CCOSI) and 22 intradomiciliary non-consanguineal contacts of patients (CNCOSI). Analysis of cytokine polymorphisms typified by the polymerase chain reaction (PCR) technique. For TGFβ, a tendency to associate the presence of the C allele at rs1982073 with leprosy was demonstrated, with the T allele being most frequently found in the CCOSI (p = .056). For the polymorphisms IL-10 we found an association of the GCC/GCC genotype with the susceptibility to the disease and the A-allele rs1800896 with the leprosy protection. Greater predominance was found of ACC / ATA (31.3%) and GCC / ATA (37.5%) (p = .03) and the A-allele rs1800896 (76.85%) (p = .043) in the CCOSI groups, while the GCC/GCC was found in the MB group (22.2%) (p = .05). For the other cytokines's SNPs there were no associations with susceptibility to leprosy.These results are limited by sample size, may not be conclusive and will need further confirmation in a larger cohort.

Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children

Background: Anaemia is a major public health concern especially in African children living in malaria-endemic regions. Interferon-gamma (IFN-γ) is elevated during malaria infection and is thought to influence erythropoiesis and iron status. Genetic variants in the IFN-γ gene (IFNG) are associated with increased IFN-γ production. We investigated putative functional single nucleotide polymorphisms (SNPs) and haplotypes of IFNG in relation to nutritional iron status and anaemia in Gambian children over a malaria season. Methods: We used previously available data from Gambian family trios to determine informative SNPs and then used the Agena Bioscience MassArray platform to type five SNPs from the IFNG gene in a cohort of 780 Gambian children aged 2-6 years. We also measured haemoglobin and biomarkers of iron status and inflammation at the start and end of a malaria season. Results: We identified five IFNG haplotype-tagging SNPs ( IFNG-1616 [rs2069705], IFNG+874 [rs2430561], IFNG+2200 [rs1861493], IFNG+3234 [rs2069718] and IFNG+5612 [rs2069728]). The IFNG+2200C [rs1861493] allele was associated with reduced haemoglobin concentrations (adjusted β -0.44 [95% CI -0.75, -0.12]; Bonferroni adjusted P = 0.03) and a trend towards iron deficiency compared to wild-type at the end of the malaria season in multivariable models adjusted for potential confounders. A haplotype uniquely identified by IFNG+2200C was similarly associated with reduced haemoglobin levels and trends towards iron deficiency, anaemia and iron deficiency anaemia at the end of the malaria season in models adjusted for age, sex, village, inflammation and malaria parasitaemia. Conclusion: We found limited statistical evidence linking IFNG polymorphisms with a risk of developing iron deficiency and anaemia in Gambian children. More definitive studies are needed to investigate the effects of genetically influenced IFN-γ levels on the risk of iron deficiency and anaemia in children living in malaria-endemic areas.

IFN-γ and TNF-α Gene Polymorphisms in Multiple Sclerosis Patients in Northwest Iran.

Cytokines are polypeptides that play critical roles in immune responses. Gene polymorphisms occurring in the inflammatory cytokines are taking a role in autoimmune diseases, including multiple sclerosis (MS), which may induce inappropriate immune responses. The aim of this study was to investigate the allelic and genotypic frequencies of interferon gamma gene (IFN-γ) at +874A/T locus and tumor necrosis factor (TNF-α) at+308A/G locus in MS patients of Azeri population. At first, a questionnaire was prepared for each of 240 healthy, non-relative, and 152 Azeri MS patients before obtaining the blood sample from all subjects. After DNA extraction, the frequency of alleles and genotypes of the IFN-γ and TNF-α genes at +874A/T and -308G/A loci, respectively, were determined by allele-specific PCR method. Finally, the frequencies were compared between control and MS patients by chi-square test (x2-test) and p<0.05 was considered significant. In the IFN-γ +874A/T gene single nucleotide polymorphism (SNP), the most allelic and genotypic frequencies in MS patients were the A allele, 55.26% (p=0.04) and the AT genotype, 52.63% (p=0.048). In healthy individuals, it was 65.42% for the A allele and 45.42% for the AA genotype. For the TNF-α 308 G/A SNP, the highest allelic and genotypic frequencies in MS patients were the G allele with 55.92% (p<0.001) and AG genotype with 61.84%, and in healthy subjects, the allelic and genotypic frequencies were 84.2% and 70.8% for the G allele and GG genotype, respectively. Head trauma, the infection with the herpes virus and Mycoplasma pneumonia, frequent colds and high consumption of canned foods provide grounds for MS. The T allele in the IFN-γ gene (+874) and the genotypes of AA and AG at the TNF-α gene (-308) at the position-308 were considered as potential risk factors for MS. Therefore, the polymorphisms in cytokine genes and following changes in their expression levels can be effective in susceptibility to MS.

Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children.

Background: Anaemia is a major public health concern especially in African children living in malaria-endemic regions. Interferon-gamma (IFN-γ) is elevated during malaria infection and is thought to influence erythropoiesis and iron status. Genetic variants in the IFN-γ gene (IFNG) are associated with increased IFN-γ production. We investigated putative functional single nucleotide polymorphisms (SNPs) and haplotypes of IFNG in relation to nutritional iron status and anaemia in Gambian children over a malaria season. Methods: We used previously available data from Gambian family trios to determine informative SNPs and then used the Agena Bioscience MassArray platform to type five SNPs from the IFNG gene in a cohort of 780 Gambian children. We also measured haemoglobin and biomarkers of iron status and inflammation at the start and end of a malaria season. Results: We identified five IFNG haplotype-tagging SNPs ( IFNG-1616 [rs2069705], IFNG+874 [rs2430561], IFNG+2200 [rs1861493], IFNG+3234 [rs2069718] and IFNG+5612 [rs2069728]). The IFNG+2200C [rs1861493] allele was associated with reduced haemoglobin concentrations (adjusted β -0.44 [95% CI -0.75, -0.12]; Bonferroni adjusted P = 0.03) and a trend towards iron deficiency compared to wild-type at the end of the malaria season in multivariable models adjusted for potential confounders. A haplotype uniquely identified by IFNG+2200C was similarly associated with reduced haemoglobin levels and trends towards iron deficiency, anaemia and iron deficiency anaemia at the end of the malaria season in models adjusted for age, sex, village, inflammation and malaria parasitaemia. Conclusion: We found limited statistical evidence linking IFNG polymorphisms with a risk of developing iron deficiency and anaemia in Gambian children. More definitive studies are needed to investigate the effects of genetically influenced IFN-γ levels on the risk of iron deficiency and anaemia in children living in malaria-endemic areas.

IFN-γ +874T/A polymorphism increases susceptibility to post-traumatic osteomyelitis.

Immunological inflammatory reaction is one of the key links in the occurrence and development of post-traumatic osteomyelitis after microbial invasion. Growing evidence suggests complex interactions between IFN-γ and bone remodelling cells. However, potential association of IFN-γ gene polymorphism with susceptibility to post-traumatic osteomyelitis remains unclear. This study aimed to investigate the potential link between IFN-γ +874T/A polymorphism and risk of developing post-traumatic osteomyelitis. A total of 189 patients with post-traumatic osteomyelitis and 200 healthy controls were enrolled for genotyping using the SNaPshot genotyping method. Statistically significant associations were found between the gene polymorphism and the risk of post-traumatic osteomyelitis by dominant model (AA+AT vs. TT, OR=1.820, p=.017) and heterozygous model (AT vs. TT, OR=1.781, p=.029). Moreover, the frequency of mutant allele A was significantly higher in the patients than that in the healthy controls (15.07% vs. 9.25%, OR=1.742, p=.013). IFN-γ +874T/A polymorphism may contribute to the increased susceptibility to post-traumatic osteomyelitis.

Interferon-γ and interleukin-12 production in relation to gene polymorphisms in bacillus Calmette-Guérin osteitis.

Interferon-γ (IFN-γ) and interleukin-12 (IL-12) play a crucial role in the defense against mycobacteria, and in the response to bacillus Calmette-Guérin (BCG) vaccination. We have previously reported clinical and outcome data of 222 BCG osteitis cases diagnosed in 1960-1988 in Finland. The immunological and genetic reports have been based on 132 blood samples obtained in 2007-2008. We compared IFNγ rs2430561 and rs35314021, IL12A rs568408 and rs2243115, and IL12B rs3212227 single-nucleotide polymorphisms (SNP) between 132 BCG osteitis patients and 99 population-based controls. In addition, stimulated production of IFN-γ and IL-12 in cell culture was evaluated in relation to the presence of IFNγ and IL12 wild versus variant genotypes, respectively. The distributions of IFNγ rs2430561, IFNγ rs35314021, IL12A rs568408, IL12A rs2243115 and IL12B rs3212227 SNP did not differ between BCG osteitis patients and Finnish population-based controls. For IFNγ rs2430561, IFNγ rs35314021 and IL12A rs2243115, the negative result was confirmed by comparing the minor allele frequencies (MAF) in BCG osteitis cases with those in the publicly available genome aggregation database, including data for 3,472 Finnish persons. Instead, for IL12A rs568408 and IL12B rs3212227, the comparison of MAF in BCG osteitis cases with those in population-based and in aggregation-based controls gave conflicting results. The presence of the wild versus variant genotype had no significant association with IL-12 or IFN-γ production in BCG-stimulated cell cultures. IFNγ gene polymorphisms did not show any association with BCG osteitis after newborn vaccination.

Searching for the Role of the IFNγ rs2430561 Polymorphism in Inducible Inflammation: Contribution to Metabolic Syndrome in 45 to 60-Year-Old Women.

Metabolic syndrome (MetS) is a cluster of conditions, increasing the risk of developing diseases that can lead to premature death. Interferon γ-inducible (the production of which is dependent on the IFNγ rs2430561 polymorphism) tryptophan-kynurenine inflammatory cascade helps to understand the increased association between inflammatory process and MetS, which is why we seek the relationship between the IFNγ gene polymorphisms and serum levels of markers of interferon-gamma (IFNγ)-inducible inflammatory cascade. The study sample consisted of 416 women, including 118 (28.4%) with MetS. The research procedure involved interview, anthropometric measurements, and blood collection. Kynurenine levels were significantly higher in the group of women with MetS. In the group with MetS, the A/T genotype of the IFNγ gene was accompanied by higher kynurenine levels. A direct relationship between the IFNγ gene polymorphisms and the rest of the markers of IFNγ-inducible inflammatory cascade was not confirmed with regard to MetS in 45 to 60-year-old women. A disparity in the kynurenine level, as well as the relationship between the presence of the A/T genotype of the IFNγ gene and a higher level of kynurenine in the group of women with MetS, may indicate an association between inflammation, metabolic disorders and tryptophan-kynurenine inflammatory cascade.

Toxoplasmic retinochoroiditis: The influence of age, number of retinochoroidal lesions and genetic polymorphism for IFN-γ +874 T/A as risk factors for recurrence in a survival analysis.

PurposeTo analyze risk factors for recurrent toxoplasmic retinochoroiditis.DesignSingle center prospective case series.Population and MethodsA total of 230 patients with toxoplasmic retinochoroiditis were prospectively followed to assess recurrences. All patients were treated with a specific drug regime for toxoplasmosis in each episode of active retinochoroiditis. Individuals with chronic diseases and pregnant women were excluded. Survival analysis by extended Cox regression model (Prentice-Williams-Peterson counting process model) was performed to evaluate the time between recurrences according to some potential risk factors: age, number of retinochoroidal lesions at initial evaluation, sex and interferon gamma +874 T/A gene polymorphism. Hazard Ratios (HR) and 95% confidence intervals (CI) were provided to interpret the risk effects.ResultsOne hundred sixty-two recurrence episodes were observed in 104 (45.2%) patients during follow-up that lasted from 269 to 1976 days. Mean age at presentation was 32.8 years (Standard deviation = 11.38). The risk of recurrence during follow up was influenced by age (HR = 1.02, 95% CI = 1.01–1.04) and number of retinochoroidal lesions at the beginning of the study (HR = 1.60, 95% CI = 1.07–2.40). Heterozygosis for IFN-γ gene polymorphism at position +874 T/A was also associated with recurrence (HR = 1.49, 95% CI = 1.04–2.14).ConclusionThe risk of ocular toxoplasmosis recurrence after an active episode increased with age and was significantly higher in individuals with primary lesions, which suggests that individuals with this characteristic and the elderly could benefit from recurrence prophylactic strategies with antimicrobials. Results suggest an association between IFN-γ gene polymorphism at position +874T/A and recurrence.

Lack of Association Between TNF-α, IFN-γ, IL-10 Gene Polymorphisms and Rheumatic Heart Disease in South Indian Population

Background: Proinflammatory and anti-inflammatory cytokines play a crucial role in the development and maintenance of immune mediated inflammatory diseases including rheumatic heart disease (RHD). Polymorphisms in tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-10 genes influence the differential cytokine expression as well as the pathogenesis of various inflammatory and autoimmune diseases. Objective: The aim of the study is to investigate the association between TNF-α, IFN-γ, and IL-10 gene polymorphisms and RHD in South Indian population. Materials and Methods: TNF-α (–308, –238), IFN-γ (+874), and IL-10 (–1082, –819, –592) gene polymorphisms were determined in 100 patients with RHD and 127 healthy siblings by PCR. Results: There was no significant difference in the genotype, allele, and haplotype frequencies of TNF-α, IFN-γ, and IL-10 polymorphisms between RHD patients and healthy siblings. Conclusion: The present study suggests that TNF-α, IFN-γ, and IL-10 gene variants may not be associated with the development of RHD in South Indian population.

The relationship between IFN-γ and TNF-α gene polymorphisms and brucellosis: Meta-analysis

Brucellosis is an infectious disease and one of the major public health problems worldwide. Several current studies have provided data that polymorphisms in the interferon-gamma gene (IFN-γ) and tumor necrosis factor-alpha gene (TNF-α) are related to brucellosis. The aim of this study was to investigate the relationship between IFN-γ +874 A/T, IFN-γ UTR5644 A/T, TNF-α -308 G/A, and TNF-α -238 G/A single nucleotide polymorphisms (SNPs) and brucellosis risk by meta-analysis. We performed a comprehensive search of the PubMed, MEDLINE, EMBASE, Web of Science, and Elsevier Science Direct databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of association between IFN-γ and TNF-α polymorphisms and brucellosis risk. A total of 17 studies including 1,904 cases and 2,233 controls fulfilled the inclusion criteria. Our pooled analysis demonstrated that the IFN-γ +874 AT vs AA genotype in a codominant model may confer an increased risk of brucellosis in the overall population (p = 0.001; OR = 0.51). Regarding TNF-α -308 G/A, our pooled analysis revealed that the AA vs GG + GA (recessive) genotype increased the risk of brucellosis (p = 0.02; OR = 2.00). In summary, our pooled analysis suggested that the IFN-γ +874 AT vs AA as well as the TNF-α -308 AA vs GG + GA genotypes demonstrated a trend for the association with a higher risk of brucellosis.