title: Genetic susceptibility to SLE is associated with TNF-alpha gene polymorphism -863, but not -308 and -238, in Thai population.
abstract: 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.
authors.affiliation: Lupus Research Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. fmednpt@md.chula.ac.th
authors.forename: N
authors.initials: N
authors.lastname: Hirankarn
authors.forename: Y
authors.initials: Y
authors.lastname: Avihingsanon
authors.forename: J
authors.initials: J
authors.lastname: Wongpiyabovorn
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013785:Thailand; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha