Abstract:
Systemic lupus erythematosus (SLE) is an autoimmune disease, which both genetic and environmental factors are believed to be involved. Many genetic studies, mostly in Caucasian, by linkage analysis and association study implicated that various genes are related to SLE. However, it is still not well understood what genes really important to SLE. TGFβ2 gene, located on chromosome lq41, is one of the candidated gene. This gene product belongs to TGFβ family, which has important role as multifunctional cytokine in tissue repair, inflammation and immunoregulation especially as an immunomodulator and immunosuppressor. Many studies in glomerulonephritis suggest that TGFβ has important role in a process of renal fibrosis and chronic kidney disease. The aim of this study was to characterize the polymorphisms of TGFβ2 gene in 153 SLE patients compared with 133 control group inorder to determine the association with disease susceptibility and disease progression especially with lupus nephritis. Four SNPs identified by THAlSNP project were included in this study located in 5‘UTR, intron 1, intron 5 and intron 6. Three of them were new markers which never been studied before. We found that the common allele _ at position +7l_72insACAA, allele T at position +720(T/G) and common allele _ at position +94400_94401insA were associated with the increased risk of SLE disease (p = 0.02, OR = 1.83, 95%Cl = 1.09-3.08, p = 0.01, OR = 2.37, 95%Cl = 1.19-4.77 and p = 0.00008, OR = 2.91, 95%Cl = 1.66-5.15, respectively). Furthermore, haplotype analysis at 4 position reveal a strongest association in _/T/A/_ haplotype with SLE susceptibility in Thai population (p = 0.0001, OR = 2.64, 95°/CI = 1.58-4.42). No association with clinical manifestation was observed. This is the first report of a very strong association of TGFβ2 gene polymorphism at intron6 with SLE susceptibility. According to the putative non-functional of this polymorphism. This observation is likely due to linkage disequilibrium to other causative polymorphism or mutation within this specific haplotype: _/T/A/_.
