RESUMO
Susceptibility to tuberculosis may be influenced by variations in human genes. The P2X7 receptor is an ATP-gated cation channel expressed in immune cells, and it influences the release of proinflammatory cytokines from monocytes and macrophages. In the present study, we aimed to evaluate the impact of P2X7 gene rs2393799 (-762T/C) and rs1718119 (Thr348Ala) polymorphisms on patient susceptibility to pulmonary tuberculosis (PTB) in a sample of the Iranian population. This case-control study was performed using 150 PTB cases and 150 controls. P2X7 receptor polymorphisms were determined using tetra-amplification refractory mutation system-polymerase chain reaction. Genotype and allelic frequencies of the rs2393799 variant within the P2X7 gene were significantly higher in the PTB patients than in the healthy controls. The genotypes were CC in 71, CT in 54, and TT in 25 PTB patients. The genotypes were CC in 104, CT in 40, and TT in 6 healthy controls. The results indicate a significant association between rs2393799 polymorphism of the P2X7 gene and susceptibility to PTB (CT vs CC: OR = 6.5, 95%CI = 2.5-16.9, P < 0.0001; TT vs CC: OR = 3.3, 95%CI = 1.2-8.9, P = 0.018; TC+TT vs CC: OR = 2.56, 95%CI = 1.59-4.12, P < 0.0001). The rs2393799 T allele is a risk factor for predisposition to PTB (OR = 2.53, 95%CI = 1.73-3.71, P < 0.0001). No association between the rs1718119 polymorphism and PTB was found. In conclusion, the rs2393799 polymorphism in the P2X7 gene may contribute to patient susceptibility to PTB in our study population.
Assuntos
Povo Asiático/genética , Receptores Purinérgicos P2X7/genética , Tuberculose Pulmonar/genética , Alelos , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de RiscoRESUMO
The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, which encodes an intracellular lymphoid-specific phosphatase, is considered an important regulator of T-cell activation. We investigated a possible association between the PTPN22 C1858T (R620W) polymorphism and pulmonary tuberculosis in an Iranian population. Single nucleotide polymorphisms of PTPN22 C1858T (rs2476601) were genotyped in 172 pulmonary tuberculosis cases and 204 normal subjects from Zaheden, Iran. Frequencies of genotypes CC, CT and TT of the PTPN22 C1858T polymorphism were 98.3, 1.7 and 0% in the pulmonary tuberculosis patients, and 96.1, 3.9 and 0% in the control group, respectively (P = 0.239). The frequency of the minor (T) allele was 0.8% in pulmonary tuberculosis patients and 2.0% in controls. Significant differences were not observed in genotype or allele frequencies of PTPN22 C1858T in the comparison between pulmonary tuberculosis patients and healthy subjects in our Iranian population sample.
Assuntos
Polimorfismo Genético , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Tuberculose Pulmonar/genética , Sequência de Bases , Estudos de Casos e Controles , Primers do DNA , Feminino , Humanos , Irã (Geográfico) , Masculino , Reação em Cadeia da Polimerase , Tuberculose Pulmonar/enzimologiaRESUMO
Concerning the key role of interferon-γ (IFN-γ) in the protective immunity against Mycobacterium tuberculosis, we aimed to find the possible association between single nucleotide polymorphism of IFN-γ +874T/A (rs61923114) and pulmonary tuberculosis (PTB). This case-control study was performed on 142 PTB patients and 166 healthy subjects. Genotype analysis was done using amplification refractory mutation system-PCR (ARMS-PCR). We found that the AA genotype of +874A/T IFN-γ is a risk factor for PTB (OR = 3.333, 95% CI = 1.537-7.236, p=0.002). The results showed that the +874A allele frequency was higher in PTB than in normal subjects (OR = 1.561, 95% CI = 1.134-2.480, p=0.007). In conclusion, significant association was found between the IFN-γ +874T/A polymorphism (rs61923114) and susceptibility to PTB in a sample of Iranian population.
Assuntos
Interferon gama/genética , Polimorfismo de Nucleotídeo Único , Tuberculose Pulmonar/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-IdadeRESUMO
Approximately 5-10% of subjects infected with Mycobacterium tuberculosis develop active tuberculosis. It has been proposed that genetic factors determine the host's vulnerability to tuberculosis. Chemokine (C-C motif) ligand 2 (CCL2), commonly known as monocyte chemoattractant protein-1 (MCP-1), plays a key role in protective immunity against M. tuberculosis. The present study was aimed to determine if there was an association between -2581 A/G single nucleotide polymorphism of CCL2 and pulmonary tuberculosis (PTB) in a sample of Iranian subjects. This case-control study was performed on 142 PTB and 166 healthy subjects. The polymorphism of CCL2 (rs1024611) was determined using tetra amplification refractory mutational system-polymerase chain reaction (tetra ARMS-PCR). There were no significant differences between PTB patients and control subjects regarding -2581 A/G single nucleotide polymorphism of CCL2. In conclusion, our results do not support an association of -2581 A/G polymorphism of CCL2 with PTB susceptibility.