title: The NRAMP1, VDR, TNF-α, ICAM1, TLR2 and TLR4 gene polymorphisms in Iranian patients with pulmonary tuberculosis: A case-control study.
abstract: The innate immune response drives early events in Mycobacterium tuberculosis infection. Since human genetic variation is an important determinant in the outcome of infection with M. tuberculosis, we typed polymorphisms in the innate immune molecules, such as natural-resistance-associated macrophage protein 1 (NRAMP1), Vitamin D receptor (VDR), Tumor necrosis factor alpha (TNF-α), intercellular adhesion molecule1 (ICAM-1), Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) in a case-control study of pulmonary tuberculosis in Iranian population. We conducted an association study and included 96 patients and 122 matched healthy individuals. We used single ARMS-PCR technique to simultaneously genotype fourteen polymorphisms in this survey. Among all fourteen polymorphisms that were examined, three polymorphisms were significantly different between case and control groups. The TNF -308A polymorphism showed significant increase in allele and genotype frequencies among patients compared to control individuals [-308A allele: 19.3 vs. 9.4%, GA genotype: 28.1 vs. 17.2%, AA genotype: 5.2 vs. 0.8%; Corrected P (Pc)<0.05], and the TLR4 variant allele and genotypes prevalence (D299G and T399I) were significantly higher among patients compared to controls [DG genotype: 14.6 vs. 5.7%, Pc<0.05 and I399 allele: 4.2 vs. 0.8%, TI genotype: 8.3 vs. 1.6%; Pc<0.05], respectively. In conclusion, our data suggest that TLR4 (D299G and T399I) and TNF (-308G/A) genetic polymorphisms may influence the risk of developing tuberculosis after exposure to Mycobacterium.
authors.affiliation: Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran; Gerash Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Jafari
authors.affiliation: Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Nasiri
authors.affiliation: Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Roozbeh
authors.initials: R
authors.lastname: Sanaei
authors.affiliation: Mycobacteriology Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Saber
authors.initials: S
authors.lastname: Anoosheh
authors.affiliation: Mycobacteriology Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Parisa
authors.initials: P
authors.lastname: Farnia
authors.affiliation: Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Adel
authors.initials: A
authors.lastname: Sepanjnia
authors.affiliation: Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran. Electronic address: tajik.n@iums.ac.ir.
authors.forename: Nader
authors.initials: N
authors.lastname: Tajik
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007492:Iran; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D018799:Intercellular Adhesion Molecule-1; D018167:Receptors, Calcitriol; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000099173:Natural Resistance-associated Macrophage Protein 1; C573420:ICAM1 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C439524:TNF protein, human; C579457:VDR protein, human
keywords: ARMS-PCR; Association study; Gene polymorphism; Iran; Pulmonary tuberculosis