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

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.

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.

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.

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.