IFN-γ +874 A>T (rs2430561) gene polymorphism and risk of pulmonary tuberculosis: a meta-analysis

Abstract

Introduction: The role of interferon gamma (IFN-γ) +874 A>T (rs2430561) gene polymorphism has been evaluated in different ethnicities with pulmonary tuberculosis (PTB) infection, and inconsistent results have been reported. In this study, a meta-analysis was performed to determine the precise association between IFN-γ +874 A>T gene polymorphism and PTB susceptibility.

Material and methods: A total of 21 studies comprising 4281 confirmed PTB cases and 5186 healthy controls were included in this meta-analysis by searching the PubMed (Medline), EMBASE, and Google Scholar web-databases.

Results: We observed reduced risk of PTB in allelic contrast (T vs. A: p = 0.001; OR = 0.818, 95% CI: 0.723-0.926), homozygous (TT vs. AA: p = 0.017; OR = 0.715, 95% CI: 0.543-0.941), heterozygous (AT vs. AA: p = 0.002; OR = 0.782, 95% CI: 0.667-0.917), dominant (TT+AT vs. AA: p = 0.002; OR = 0.768, 95% CI: 0.652-0.906), and recessive (TT vs. AA+AT: p = 0.042; OR = 0.802, 95% CI: 0.649-0.992) genetic models. In ethnicity-wise subgroup analysis, reduced risk of PTB was found in the Caucasian population. However, we did not find an association with any of the genetic models in the Asian population.

Conclusions: In conclusion, the IFN-γ +874 A>T gene polymorphism is significantly associated with reduced risk of PTB, showing a protective effect in the overall and in the Caucasian population. However, this polymorphism is not associated with PTB risk in the Asian population.

Keywords: genetic model; interferon-γ; meta-analysis; polymorphism; pulmonary tuberculosis.

Figure 1

PRISMA Flow-diagram showing identification and selection of the studies for this metaanalysis

Figure 2

A – Sensitivity analysis to evaluate the influence of each study on the pooled OR by deleting a single study each time for the overall analysis (allelic contract (T vs. A), homozygous (TT vs. AA) and heterozygous (AT vs. AA) genetic models). Black squares represent the value of OR, and the size of the square indicates the inverse proportion relative to its variance. The horizontal line is the 95% CI of OR. B – Sensitivity analysis to evaluate the influence of each study on the pooled OR by deleting a single study each time for the overall analysis (dominant (TT+AT vs. AT) and recessive (TT vs. AA+AT) genetic models). The black squares represent the value of OR, and the size of the square indicates the inverse proportion relative to its variance. The horizontal line is the 95% CI of OR

Figure 3

A – Forest plot of OR with 95% CI of PTB risk associated with the IFN-γ +874 A>T gene polymorphism for overall population (allelic contract (T vs. A), homozygous (TT vs. AA), heterozygous (AT vs. AA) genetic models). The black square represents the value of OR, and the size of the square indicates the inverse proportion relative to its variance. The horizontal line is the 95% CI of OR. B – Forest plot of OR with 95% CI of PTB risk associated with the IFN-γ +874 A>T gene polymorphism for the overall population (dominant (TT+AT vs. AT), recessive (TT vs. AA+AT) genetic models). The black square represents the value of OR, and the size of the square indicates the inverse proportion relative to its variance. The horizontal line is the 95% CI of OR

Figure 4

Forest plots of ORs with 95% CI of PTB risk associated with the IFN-γ +874 A>T gene polymorphism in the Asian population (allelic contract (T vs. A), homozygous (TT vs. AA), heterozygous (AT vs. AA), dominant (TT+AT vs. AT), recessive (TT vs. AA+AT) genetic models). The black square represents the value of OR, and the size of the square indicates the inverse proportion relative to its variance. The horizontal line is the 95% CI of OR

Figure 5

Forest plots of ORs with 95% CI of PTB risk associated with the IFN-γ +874 A>T gene polymorphism in the Caucasian population (allelic contract (T vs. A), homozygous (TT vs. AA), heterozygous (AT vs. AA), dominant (TT+AT vs. AT), recessive (TT vs. AA+AT) genetic models). The black square represents the value of OR, and the size of the square indicates the inverse proportion relative to its variance. The horizontal line is the 95% CI of OR