Study On TRAIL Gene Polymorphism In Patients With Systemic Lupus Erythematosus

BackgroundTumour necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) was found and named by Wiley in 1995. TRAIL is mapped at the long arm of chromosome 3q26 in humans. It is composed of five exons. It encodes approximately 1.77 kb mRNA. TRAIL is a new identified member of the TNF superfamily, and its structure is similar to other TNF family members. It preferentially induces apoptosis of various abnormal cells. By combining with its receptor, TRAIL can induce apoptosis and play other biological effects. It has been reported that TRAIL is associated with the pathogenesis of some autoimmune diseases such as Sjogren syndrome, autoimmune encephalomyelitis,multiple sclerosis,and thyroid disease.Systemic lupus erythematosus (SLE) is a wide range of tissue and organ involvement of an autoimmune disease. Its etiology and pathogenesis have not been entirely investigated clearly. It is characterized by B-cell hyperactivity, autoantibody production, and immune complex deposition in multiple organs.Recent studies using microarrays showed higher expression of TRAIL mRNA in PBMC from SLE patients. Serum sTRAIL levels increased in SLE patients,which indicated that abnormal expression of TRAIL was related to the development of SLE. However, the association between TRAIL gene polymorphism and the pathogenesis of SLE has never been evaluated. The present study aims to explore the relationship between TRAIL gene polymorphism and the pathogenesis of SLE and expects to find the new susceptibility gene of SLE.We hope to provide more experimental data to prove TRAIL gene involvement in the development of SLE.ObjectiveTo disclose the relationships between TRAIL gene polymorphism in the 3' -untranslated region at 1525 and 1595 sites in patients with SLE.MethodsThis study followed a case-control design. We choosed 167 unrelated patients with SLE according to American Rheumatism Association diagnostic criteria and 190 healthy controls to study. Blood samples were harvested and genome DNA was extracted using phenol chloroform method. The polymorphisms of TRAIL gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods in 167 patients with SLE and 190 healthy controls. The differences in the sex ratio and age between patients and controls were not significant.Results1. The genotype frequencies of TRAIL at 1525 and 1595 in all subjects were the same.2. Genotype frequencies of 1525GG/1595CC,1525GA/1595CT,1525AA/1595TT were 23.3%,54.6%,22.1% in the healthy controls and 35.3%,50.3%,14.4% in the SLE patients separately. The TRAIL genotype and allele frequencies of the SNPs in SLE patients were significantly higher than the healthy controls.ConclusionTRAIL gene polymorphisms at 1525 and 1595 sites exist in Chinese population. And the SNPs were the same. The frequency of CC/GG at position 1595 /1525 homozygote in SLE patients was significantly higher than that of in the control. The C/G allele frequencies in SLE patients were significantly higher than those of healthy controls. The results indicated that the presence of the CC/GG genotype at position 1595/1525 in exon 5 of TRAIL maybe represent a higher risk of SLE.