Assessment of tumor necrosis factor superfamily member 10 (TNFSF10) gene variants in systemic lupus erythematosus patients

Abstract

Aim of the work

To investigate the association between tumor necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL) 1525 G > A (TNF supefamily member 10; TNFSF10, rs1131568) and 1595 C > T (TNFSF10 rs1131580) genetic variants and systemic lupus erythematosus (SLE) susceptibility in Egyptian patients and their relationship with clinical and laboratory outcomes of the disease.

Patients and methods

A total of 123 SLE patients and 110 age- and sex-matched healthy control subjects were tested for TRAIL 1525 G > A and 1595 C > T genotyping by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP), followed by confirmation of random samples from each genotype by direct sequencing technique. Disease activity was determined using the SLE Disease Activity Index (SLEDAI).

Results

The patients were 107 females and 16 males with mean age 32.87 ± 9.6 years. The median value of SLEDAI of the patients was 18 (12–27). The two genetic variants of TRAIL, 1525 G > A and 1595 C > T, were in complete linkage disequilibrium. There was a significant increase in the frequencies of combined genotypes (GA + AA)/(CT + TT) and A/T alleles of TRAIL 1525/1595 variants among SLE cases when compared with the control group (OR = 1.7, 95 % CI = 1.0 – 2.98, p = 0.048; OR = 1.7, 95 % CI = 1.1 – 2.8, p = 0.02, respectively). Additionally, the A/T variants of TRAIL 1525/1595 were associated with higher risks of developing lupus nephritis (OR = 2.6, 95 % CI = 1.2 – 5.7, p = 0.015) and higher disease activity (OR = 3.8, 95 % CI = 1.3 – 10.9, p = 0.010).

Conclusion

TRAIL 1525 G > A and 1595 C > T gene variants confer susceptibility to SLE, which is significantly related to the clinical phenotypes of SLE and associated with higher disease activity.