Genetic susceptibility to SLE is associated with TNF-alpha gene polymorphism-863, but not -308 and -238, in Thai population

The production of cytokine varies among individuals and correlates with the polymorphism of cytokine genes. Three functional single nucleotide polymorphisms (SNPs) at position -863, -308, and -238 in the tumour necrosis factor alpha (TNF-alpha) gene promoter were analysed for association with systemic lupus erythematosus (SLE) (n = 154), and clinical manifestations in a Thai population were compared with 154 ethnically matched controls. The genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism method. The association between these SNPs and SLE was analysed using chi-squared test. The -863A allele and -863A, -308G, -238G haplotype were found to be significantly increased in SLE patients (25%) compared with healthy controls (15.3%) (Pc = 0.009, OR = 1.85, 95% CI = 1.21-2.83). In addition -863A allele was found to be significantly increased in the SLE group with Raynaud's phenomenon compared to SLE without Raynaud's phenomenon (35% vs. 19.4%) (Pc = 0.048, OR = 2.23, 95% CI = 1.21-4.10). The -863A allele of TNF-alpha gene and the extended haplotype of -863A, -308G, -238G can be used as a genetic marker for SLE susceptibility in Thai populations. In addition, the -863A genotype could produce high TNF levels and potentially induce the occurrence of Raynaud's phenomenon.