Interferon-gamma (IFN-γ) intronic variant (rs2430561) is a risk factor for systemic lupus erythematosus: Observation from a meta-analysis.

BACKGROUND: The role of interferon-gamma (IFN-γ) in autoimmune disorders has been well documented. Elevated levels of IFN-γ are observed in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and are linked with disease severity. Single nucleotide polymorphism in the intronic region of the IFN-γ gene (+874 T>A rs2430561) has been associated with susceptibility to the development of RA and SLE; however, the reports remained contradictories. We conducted a meta-analysis using earlier published articles to reach a valid conclusion on the role of IFN-γ polymorphism (+874 T>A) in autoimmune diseases. MATERIALS AND METHODS: Various online databases such as PubMed, Google Scholar, Science Direct, and Scopus were searched to find eligible reports for inclusion in the present analysis. Two independent authors extracted eligible studies and data. The meta-analysis was performed by comprehensive meta-analysis software (CMA) v.3.1. Trial sequential analysis was performed to test whether enough case-control studies have already been conducted worldwide to reach a valid observation. RESULTS: Six published reports on the role of IFN-γ +874 T>A in SLE and four in RA were found after searching various databases. However, out of those six studies in SLE, in one study, the distribution of genotypes was not following the hardy-Weinberg equilibrium. In RA, three studies were deviated out of four reports. Thus, a total of five studies comprising 1440 SLE patients and 1748 controls were considered for the present meta-analysis. Meta-analysis showed a significant association between IFN-γ +874 T>A variants with susceptibility to SLE (homozygous comparison: p = 0.036, OR = 1.592, heterozygous model: p = 0.042, OR = 1.507, dominant model: p = 0.002, OR = 1.309). CONCLUSIONS: IFN-γ +874 T>A variant is associated with predisposition to SLE development.

Correlation between interferon-γ rs2430561 single nucleotide polymorphisms and susceptibility to herpes zoster / 中华皮肤科杂志

Objective:To investigate the correlation of interferon (IFN) -γ rs2430561 single nucleotide polymorphisms (SNPs) and serum IFN-γ levels with susceptibility to herpes zoster.Methods:Blood samples were collected from 74 patients with herpes zoster and 40 healthy controls in General Hospital of Southern Theatre Command and the Fifth People Hospital of Hainan Province from November 2019 to November 2020. PCR and Sagner resequencing were conducted to detect the IFN-γ rs2430561 SNPs in the subjects, fluorescence-based quantitative PCR was performed to determine the copy number of varicella-herpes zoster virus (VZV) DNA in the serum of the patients with herpes zoster, and enzyme-linked immunosorbent assay was conducted to detect the serum IFN-γ level. Measurement data were compared by using t test or non-parametric test, and enumeration data by using chi-square test or Fisher′s exact test. Results:As rs2430561 genotyping showed, there were 4 patients with AA genotype, 37 with TT genotype and 33 with TA genotype in the herpes zoster group, as well as 13 subjects with TA genotype and 27 with TT genotype in the healthy control group, and the frequency of A allele of rs2430561 was significantly higher in the herpes zoster group (27.70%) than in the control group (16.25%, P=0.036) . The serum IFN-γ level ( M[ P25, P75]) was significantly lower in the herpes zoster group (33.45[0.80, 95.01]pg/ml) than in the control group (67.83[2.74, 318.35]pg/ml, U=1 822, P=0.028) . The VZV DNA copy number (expressed as a logarithm to the base of 10) per milliliter was 3.23 ± 0.71 in the serum of the patients with herpes zoster, and the serum IFN-γ level was negatively correlated with the VZV DNA copy number ( r=-0.302, P=0.009) . Conclusion:The carriage of rs2430561 A allele may affect the expression of IFN-γ, leading to higher susceptibility to herpes zoster.

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.

IFNG +874 A/T is associated with acute lymphoblastic leukemia in Mexican Mestizos.

Acute lymphoblastic leukemia (ALL), the most common type of cancer in children worldwide, has one of the highest incidence rates in Mexico. It is a multifactorial disease and different cytokine single nucleotide polymorphisms (SNP), have been associated with ALL expression. Few studies have been published analyzing IFNG +874 T/A and IL2 -330 G/T in this type of leukemia. These SNPs are involved in high or low expression, and are central to cellular immunity, influencing greatly tumor growth. The purpose of this work was to explore the association of IFNG +874 A/T (rs2430561) and IL2 -330 G/T (rs2069762) SNPs with ALL susceptibility and/or protection in 488 Mexican Mestizos patients, as compared to 950 Mexican Mestizo healthy controls. The results demonstrated that IFNG +874 T allele (pc = 0.00004, OR = 0.673) and the TT genotype (pc = 0.00015, OR = 0.349), protect against ALL expression with no specific gender association; however, the TT homozygote genotype (vs. TA+AA) seems more protective in males (pc = 0.00683). IL2 -330 G/T does not contribute to the development of ALL. In healthy Mexicans, the most common genotypes for IL2 and IFNG, are the low cytokine producers, suggesting that the genetic background in this ethnic group, may be partly responsible for the high incidence of ALL. These results show for the first time in Mexicans, the relevant role that IFNG SNP has in the genetic etiology of ALL. Thus, a large group of patients belonging to different ethnicities will be very helpful to study in order to demonstrate if these SNPs contribute to the genetic etiology of ALL, as shown here in Mexican Mestizos.

Genetic association of pro-inflammatory cytokine gene polymorphisms with coronary artery disease (CAD) in a North Indian population.

BACKGROUND: Cytokines regulate the expression of inflammatory molecules which destabilize the atheromatic plaques. This study focuses on studying the association of inflammatory cytokine polymorphisms like TNF-α -308 (G/A), TNF-ß +252 (A/G), IL-6 -174 (G/C) and IL-6 -597 (G/A), and IFN-É£ +874 (T/A) with coronary artery disease (CAD) among north Indian patients. MATERIALS AND METHODS: 143 CAD and 137 normal healthy controls were recruited in this study. DNA extraction was carried out by high salting out method. TNF-α -308 (G/A) (rs1800797), TNF-ß +252 (A/G) (rs909253), IL-6 -174 (G/C) (rs1800795), IL6 -597 (G/A) (rs1800797), and IFN-É£ +874 (T/A) (rs2430561) SNPs were genotyped by TaqMan®SNP genotyping assays. Different statistical analyses were performed using SPSS v 22.0 and SNPStats. p≤0.05 was considered significant. RESULTS: Significant risk association with CAD was found for TNF-α -308 (G/A) "A" allele (OR=5.6, CI 1.8-17.4, p=0.001) and TNF-ß +252 (A/G) "G" allele (OR=3.4, CI=1.9-6.0, p<0.001). However, no statistical significance was found for IL-6 -174 (G/C) or IL6 -597 (G/A), with CAD. TNF-α -308 (G/A), and TNF-ß +252 (A/G) haplotype "GG" "AG" increased CAD risk significantly (GG haplotype, adjusted OR=2.6, CI 1.4-5.0, p=0.003 and AG haplotype OR=8.5, CI 2.2-33.35, p=0.002) after adjustments for age, sex, TC, TG, HDL, APOB, smoking and diet. DISCUSSION: The present study found significant risk association for TNF-α -308 (G/A), and TNF-ß +252 (A/G) genotypes, alleles and haplotypes, with CAD in a North Indian population.

Associations of IFN-γ rs2430561 T/A, IL28B rs12979860 C/T and ERα rs2077647 T/C polymorphisms with outcomes of hepatitis B virus infection: a meta-analysis.

Several studies investigated associations of IFN-γ rs2430561 T/A, IL28B rs12979860 C/T and ERα rs2077647 T/C gene polymorphisms with outcomes of hepatitis B virus (HBV) infection, but the results were controversial. Therefore, we performed a meta-analysis of all published observational studies to address this inconsistency. Literature was searched in online database and a systematic review was conducted based on the search results. A total of 24 studies were included and dichotomous data were presented as odds ratio (OR) with a 95% confidence interval (CI). The rs2430561 T allele was associated with reduced persistent HBV infection risk (T vs. A: OR, 0.690; 95% CI, [0.490, 0.971]), while the rs2077647 T allele significantly increased the risk of persistent HBV infection (T vs. C: OR, 1.678; 95% CI, [1.212, 2.323]). Rs 2077647 CC might play a role in protecting individuals against HBV persistence (TT vs. CC: OR, 4.109; 95% CI, [2.609, 6.473]). Furthermore, carriers of the rs2430561 TT genotype were more likely to clear HBV spontaneously compared with those of the AA genotype (TT vs. AA: OR, 0.555; 95% CI, [0.359, 0.856]). For rs12979860 C/T polymorphism, no significant correlation with HBV infection outcomes was found. In subgroup analyses, the results were similar to those of overall analysis. However, for rs2077647 TT vs. TC+CC, significantly increased risks were observed in the Asian and hospital-based population, but not in the overall analysis. IFN-γ rs2430561 T/A and ERα rs2077647 T/C genetic polymorphisms were associated with outcomes of HBV infection, but no association was found between IL28B rs12979860 C/T and HBV infection.