title: Interferon gamma +874T/A polymorphism is associated with susceptibility to active pulmonary tuberculosis development in Tunisian patients.
abstract: Interferon gamma (IFN-γ) is a key cytokine involved mainly in the defense against intracellular pathogens such as Mycobacterium tuberculosis. Given its key role in the control of tuberculosis (TB), in the present article we have investigated a possible association between IFN-γ gene single-nucleotide polymorphism linked to high and low producer phenotypes (IFN-γ [+874T(high) → A(low)]) (rs2430561) and risk development of active TB in Tunisian patients. Genomic DNA samples were obtained from 223 patients with active TB (168 pulmonary and 55 extrapulmonary cases) and 150 healthy blood donors. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism method. The +874 AA genotype (low IFN-γ producer) was significantly associated with increased risk of developing of active pulmonary TB (odds ratio [OR] = 2.18; 95% confidence intervals [CI], 1.33-3.57; P corrected for the number of genotypes [Pc] = 0.003). By contrast, the AT genotype was found to be significantly associated with resistance to pulmonary TB (OR = 0.46; 95% CI, 0.28-0.74; Pc = 0.0018) and extrapulmonary TB development (OR = 0.46; 95% CI, 0.23-0.91; Pc = 0.045). Collectively, our data showed that the IFN-γ +874T/A polymorphism is a determinant in the resistance or susceptibility to the development of active TB in the studied population.
authors.affiliation: Laboratory of Microbiology and Immunology, Farhat Hached University Hospital, Av. Ibn el Jazzar, Sousse, Tunisia. wbenselma@hotmail.com
authors.forename: Walid
authors.initials: W
authors.lastname: Ben Selma
authors.forename: Hedi
authors.initials: H
authors.lastname: Harizi
authors.forename: Iheb
authors.initials: I
authors.lastname: Bougmiza
authors.forename: Naila
authors.initials: N
authors.lastname: Hannachi
authors.forename: Imen
authors.initials: I
authors.lastname: Ben Kahla
authors.forename: Radhia
authors.initials: R
authors.lastname: Zaieni
authors.forename: Jalel
authors.initials: J
authors.lastname: Boukadida
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014397:Tuberculosis, Pulmonary / Q000235:genetics*; D014416:Tunisia; D055815:Young Adult
chemical_list: D007371:Interferon-gamma