Tumor necrosis factor-alpha −308G/A gene polymorphism and novel biomarker profiles in patients with Takayasu arteritis

Abstract

Background: Takayasu arteritis (TA) is an idiopathic chronic inflammatory disease of the aorta and its branches, leading to stenosis, occlusion, and aneurysmal dilatation. Tumor necrosis factor-alpha (TNF-α) is a cytokine with pleomorphic actions and plays a pivotal role in inflammation; the serum level of TNF-α is genetically determined. However, the literature lacks adequate information on the association of TNF-α polymorphisms with TA. Hence, the present study investigates the contribution of TNF-α polymorphism toward the complex etiology of TA. Methods: A cross-sectional study was performed in 87 patients with TA and 90 controls. A promoter region polymorphism of TNF-α, rs1800629 G/A, or −308G/A was genotyped in all the study subjects followed by a case–control association study. Furthermore, to understand the biomarker profile, levels of specific markers such as erythrocyte sedimentation rate, serum high-sensitivity C-reactive protein, interleukin-18, interleukin-6, and TNF-α were measured in all the study subjects. Results: All the inflammatory markers were significantly higher in the TA patients than in the controls. The genetic study (available for 57 TA patients and 36 controls) revealed that the TNF-α −308A allele was overrepresented in the TA patients (12% vs 7%). The TNF-α −308A allele correlated with the increased TNF-α levels, but it could not attain significance because of a small sample size. Conclusion: The TNF-α −308G/A polymorphism is associated with TNF-α levels in Indian population, which might have implications for clinical risk stratification and treatment. The different TNF-α gene promoter polymorphism might contribute to the molecular pathogenesis of TA. However, further study of the underlying mechanism is warranted. Keywords: Takayasu arteritis, Biomarkers, Tumor necrosis factor-alpha, Gene polymorphism