Toll-like Receptor 4 Polymorphisms (rs4986790, rs4986791) and Serum Tumor Necrosis Factor Alpha levels in Chronic Obstructive Pulmonary Disease and Lung Cancer

Document Type : Original research articles

Authors

1 Department of Medical Microbiology and Immunology, Faculty of Medicine, South Valley University, Qena, Egypt.

2 Department of Chest Diseases and Tuberculosis, Faculty of Medicine, South Valley University, Qena, Egypt.

3 Department of Oncology and Nuclear Medicine, Faculty of Medicine, South Valley University, Qena, Egypt.

4 Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.

Abstract

Background: Genetic factors and environmental conditions have a great impact on Chronic Obstructive Pulmonary Disease (COPD) and lung cancer (LC). Toll Like Receptor 4 (TLR4) gene polymorphisms may induce airway inflammation and cancer. Elevated TNF-α serum levels in COPD and LC patients exacerbate inflammation and disease progression.
Objectives: To investigate the prevalence and type of TLR4 polymorphisms and TNF-α serum levels in COPD and LC susceptibility.
Patients and methods: Case-control study with 50 COPD, 50 LC, and 50 healthy controls aged 19–75. DNA was extracted from blood samples, and PCR-RFLP and ELISA were used to evaluate TLR4 polymorphisms (rs4986790, rs4986791) and serum TNF-alpha.
Results: Most LC patients (86%) were male compared to COPD (58%), P = 0.008. Smokers were 68% and 22% in LC and COPD patients, respectively, compared to 32% in controls (P < 0.001). Significantly, 38% of COPD patients were exposed to avian excreta compared to 0% of controls (P < 0.001). Genotyping of 896 A/G (SNP rs4986790) showed that 2% of LC patients were heterozygote with insignificance (P = 0.315) compared to control and COPD, and 4% were heterozygotes (CT) for 1196 C/T (SNP rs4986791) with insignificant (P = 0.153).
Conclusion: The genotype (AA) of TLR4 (896 A/G) represents 98% and the genotype (CC) of TLR4 (1196 C/T) represented 96% of lung cancer cases. In COPD, both the genotype (AA) of TLR4 (896 A/G) and (CC) of TLR4 (1196 C/T) represented 100%. TNF-α had a significant negative correlation with chemotherapy.

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