Relationship between tumor necrosis factor-α (TNFA) gene polymorphisms and cardiac sarcoidosis

Abstract

Identification of genetic predisposition to cardiac sarcoidosis could play a critical role in the detection of sub-clinical forms of the disease. The aim of this study was to investigate the possible correlations between the emergence of cardiac sarcoidosis and the -1.031T/C, -857C/T, -308G/A, and -238G/A Tumor Necrosis Factor-α (TNFA) polymorphisms in a well-defined Greek cohort. One-hundred and seventy-three patients of Greek origin with sarcoidosis were recruited in the present study. Cardiac sarcoidosis was determined according to established criteria. Blood samples were collected and the TNFA polymorphisms were genotyped. No significant difference was noted between the patients with cardiac involvement and those without, concerning the -1.031T/C and -238G/A TNFA polymorphisms. Regarding the -857C/T polymorphism, the TT genotype and the T allele were found to be over-represented in patients with cardiac involvement (p=0.02 and 0.012, respectively). AA genotype of the -308G/A as well as the A allele were also found significantly more frequently in patients with cardiac sarcoidosis (p=0.014 and 0.012 respectively). From the investigated TNFA promoter polymorphisms, we were able to deduce nine main haplotypes. Haplotypes 3 and 5, including A nucleotide at position -308, and T nucleotide at position -857 respectively, were significantly over-represented in the group with cardiac involvement. We detected an increased presence of genetic polymorphisms in the TNFA gene of patients with cardiac involvement. However, the role and the clinical application of these findings need further exploration.

Keywords: TNF; biomarkers; cardiac sarcoidosis; gene polymorphisms; inflammation; sarcoidosis.