Dataset Information

Polymorphism of IFN-? (+874 T/A) in Syrian patients with chronic hepatitis B.

ABSTRACT: AIM:This study aimed to investigate the association of IFN- ? +874 (T/A) polymorphism with susceptibility to chronic HBV infection in the Syrian population. BACKGROUND:Accumulating evidence indicate that the inadequate immune responses are responsible for HBV persistency. Therefore, polymorphisms in genes encoding the cytokines, which are responsible for regulation of the immune response, can affect the course and outcome of the infection. The IFN-? +874 T/A polymorphism affects the expression of IFN-?, which has been shown to be crucial to HBV clearance. METHODS:In this case-control study, 140 samples were collected (70 healthy individuals, 70 chronic HBV patients), and genomic DNA was isolated. Sequencing and ARMS-PCR were performed to genotype the IFN-? +874 T/A polymorphism. RESULTS:Results of this study showed an association between IFN- ? +874 T/A polymorphism and the susceptibility to chronic HBV infection (P < 0.05). In addition, results showed that the AA genotype increased the risk of chronicity (OR = 3.05, 95% CI = 1.35 - 6.89), whereas the AT and TT genotypes reduced the risk of chronicity (OR = 0.33, 95% CI = 0.150 - 0.753). CONCLUSION:Results of this study conclude that the IFN- ? +874 T/A polymorphism may be associated with the chronic HBV infection, according to the genetic model AA vs. AT&TT.

SUBMITTER: Al Kadi M

PROVIDER: S-EPMC5346822 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Polymorphism of IFN-γ (+874 T/A) in Syrian patients with chronic hepatitis B.

Al Kadi Mohamad M Monem Fawza F

Gastroenterology and hepatology from bed to bench 20170101 1

<h4>Aim</h4>This study aimed to investigate the association of IFN- γ +874 (T/A) polymorphism with susceptibility to chronic HBV infection in the Syrian population.<h4>Background</h4>Accumulating evidence indicate that the inadequate immune responses are responsible for HBV persistency. Therefore, polymorphisms in genes encoding the cytokines, which are responsible for regulation of the immune response, can affect the course and outcome of the infection. The IFN-γ +874 T/A polymorphism affects t ...[more]

PMID: 28331562

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Project description:IntroductionTuberculosis (TB) is now the 2nd leading infectious killer after COVID-19 and the 13th leading cause of death worldwide. Moreover, TB is a lethal combination for HIV-patients. Th1 responses and particularly IFN-γ are crucial for immune protection against Mycobacterium tuberculosis infection. Many gene variants for IFNG that confer susceptibility to TB have been described in multiple ethnic populations. Likewise, some epigenetic modifications have been evaluated, being CpG methylation the major epigenetic mark that makes chromatin inaccessible to transcription factors, thus avoiding the initiation of IFNG transcription.MethodsWe evaluated both genetic and epigenetic changes involved in IFN-γ production and TB susceptibility in Argentine population. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was performed for the IFN-γ +874 A/T polymorphism (rs2430561) genotyping in 199 healthy donors (HD) and 173 tuberculosis (TB) patients. IFN-γ levels from M. tuberculosis-stimulated PBMCs were measured by ELISA. The methylation status at the -53 CpG site of the IFNG promoter in individuals with latent infection (LTBI), TB and HD was determine by pyrosequencing.ResultsUsing a case-control study, we found that A allele and, consequently, AA genotype were overrepresented in patients with active disease. Moreover, HD carrying T allele (AT or TT genotype) evidenced an augmented IFN-γ secretion compared to TB patients. Codominance was the genetic model that best fits our results according to the Akaike information criterion (AIC). In addition, increased methylation levels at the -53 CpG site in the IFN-γ promoter were observed in whole blood of patients with active TB compared to LTBI individuals.DiscussionIFN-γ is regulated by genetic variants and epigenetic modifications during TB. Besides, AA genotype of the rs2430561 single nucleotide polymorphism could be considered as a potential TB susceptibility genetic biomarker in Argentina and the methylation of the -53 CpG site could result in a useful predictor of TB reactivation.

Project description:According Global Cancer Statistics 2020 GLOBOCAN estimates female breast cancer was found as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), and the fourth leading cause (6.9%) of cancer death among women worldwide. Identification of new diagnostic marker sharply characterize the tumor feature is intensive need. The present work was performed to investigate the involvement of the INF-γ + 874 T/A gene polymorphism in different breast cancer prognostic factors. Polymorphism detection analysis was performed on 163 subjects from breast cancer patients, 79 with inflamed cells of breast patients and 144 controls. The gene polymorphism was detected using the amplification refractory mutation system- polymerase chain reaction method (ARMS-PCR). The distribution of INF-γ T + 874A gene polymorphism shows strong significant association between INF-γ + 874 T/A genotypes TT in BC patients (ORTT: 6.41 [95% CI = 2.72-15.1] P < 0.0001) as well as strong significant association regarding T allele (ORT: 1.99 [95% CI = 1.43-2.76] P < 0.0001) when compared to the healthy control. In ICB group the strong association was noted with INF-γ + 874 T/A genotypes AT genotype (ORAT: 2.28 [95% CI = 1.22-4.29] P = 0.007). From the different histological BC hormonal markers the human epidermal growth factor receptor 2 (HER2) was showing significant association in INF-γ + 874 T/A genotypes TT (P = 0.03) and recessive model (TT versus AA + AT P = 0.03). Concerning different BC prognostic models, the poor prognostic one of luminal B, (ER+ve PR+ve Her2+ve) show significant association in the host INF-γ + 874 T/A genotype (TT, P = 0.03) and recessive model (TT versus AA + AT P = 0.02) when compared to the good prognostic hormonal status luminal A model, (ER+ve PR+ve Her2-ve). It seems that this is the first study that interested in correlate the INF-γ + 874 T/A gene polymorphisms in Egyptian BC patients. T allele, TT genotype and recessive model of the INF-γ + 874 T/A gene variants were documented as risk factors for BC pathogenesis. It may be used as practical biomarker to guide the BC carcinogenesis and risk process.

Dataset Information

Polymorphism of IFN-? (+874 T/A) in Syrian patients with chronic hepatitis B.

Publications

Polymorphism of IFN-γ (+874 T/A) in Syrian patients with chronic hepatitis B.

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