TGFB2 Gene

Abstract: Background: TGF-β2 has a role in immune regulation, and genetic variance within the gene might contribute to systemic lupus erythematosus (SLE) pathogenesis. The TGFB2 gene is one candidate gene within the major SLE genetic susceptibility loci. Objective: Investigate the TGFB2 gene located on chromosome 1q41 as a SLE susceptibility gene. Materials and methods: One hundred fifty three SLE patients and 133 healthy controls participated in this study. Four markers selected in two haplotype blocks that have a minor allele frequency greater than 5% in Thai population were genotyped and analyzed in the association study. Results: There was no significant association between SLE susceptibility and the polymorphism in the promoter area (+67_68insACAA) and +89835 (A/G) at the intron 5 of TGFB2 gene. Instead, minor allele of the two new genetic markers at the intron 1 (+720) (corrected p-value = 0.024, OR = 0.4141, 95%CI = 0.22-0.80) and intron 6 (+94399_94400) (corrected p-value = 0.000143, OR = 0.3367, 95%CI = 0.20-0.58) were independently associated as a protective factor to SLE. Additionally, the real time RT-PCR results showed that patients with the protective allele (minor allele) at the +94399_94400 position have higher TGF-β2 mRNA level in leukocytes than patients with the risk allele (p=0.011). Conclusion: Two new genetic markers at intron1 (+720) and intron 6 (+94399_94400) were independently associated with SLE. The observed results have to be confirmed in other populations with a large sample size.

Abstract: Animal studies have shown that knockout of the transforming growth factor beta-2 (TGFb2) gene results in diverse cardiovascular malformations and that its unregulated expression is involved in the pathogenesis of heart defects However, little information is available on the genetic and expression alternations of the TGFb2 gene in children with congenital heart disease This study investigated the genotype and expression of the TGFb2 gene in children with congenital conotruncal defects (CTDs) The whole coding region of the TGFb2 gene was sequenced in 400 children with CTD The mRNA and protein expression of the TGFb2 gene was further analyzed in the myocardial tissues of 37 children with CTD and 5 age-matched healthy children using real-time polymerase chain reaction and immunohistochemistry No pathogenic mutations in the coding region of the TGFb2 gene were shown by DNA sequencing except for a silent mutation (c597T ( C) in exon 4 of one patient The TGFb2 expression at either the mRNA or the protein level in the myocardial tissues did not differ significantly between the children with CTD and the children without heart defects The results indicate that germline mutation of the TGFb2 gene is not a common cause of CTD in humans and that the TGFb2 expression level may be less critical in humans than in animals for the pathogenesis of CTD