Clinical significance of tumor necrosis factor-α-863 C/A and -1031 T/C promoter polymorphisms in systemic lupus erythematosus patients: Relation to disease activity and damage

Abstract Aim of the work To assess the clinical significance of serum levels of tumor necrosis factor alpha (TNF-α) and its -863 C/A and 1031 T/C promoter polymorphism in systemic lupus erythematosus (SLE) patients and find any association to disease activity and damage. Patients and methods Forty-two female SLE patients and 30 age and gender matched healthy control were included. Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaboration Clinics-damage index were assessed. Serum TNF-α levels were measured and genotyped for TNF-α-863 C/A and 1031 T/C promoters. Results The SLE patients had a mean age of 28.5 ± 7.6 years and disease duration 3.3 ± 2.9 years. The mean serum TNF-α level in the SLE patients (8.2 ± 9.8 pg/ml) was significantly higher than in the control (3.5 ± 2.6 pg/ml) (p = 0.005). The TNF-α-863AA genotype was significantly frequent (52.4%) in the SLE patients compared to control (23.3%) (p = 0.012). Those patients had a significantly increased proteinuria and a tendency to a higher serum TNF-α level. Patients with TNF-α-1031 CC genotype had a significantly increased serum TNF-α levels (p = 0.002) and frequency of mucocutaneous manifestations (p = 0.03) as well as a higher frequency of lupus nephritis (LN) compared to those with TT genotype (p = 0.04). Only serum TNF-α level would predict the disease activity. Conclusion TNF-α-863 promoter gene polymorphism may be considered as a genetic marker for SLE susceptibility and its AA genotype was associated with LN and with high serum TNF-α production. The TNF-α-1031 AA genotype was related to an increased serum TNF-α level as well as to mucocutaneous manifestations and LN.