Novel genetic marker in TGFB2 gene associated with expression of TGF-?2 in leukocyte and SLE susceptibility

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.

Pharmacokinetic studies of cyclosporin in Thai kidney transplantation patients.

Pharmacokinetic studies were performed in 10 Thai patients with kidney transplantation who received microemulsion formulation (Neoral) of cyclosporin A (CsA) twice daily. No agents having pharmacokinetic effect on CsA had been used in these patients. The mean values of 12-h AUC (area under the concentration-blood curve) were 4603.63 +/- 344.61 ng x h/ml. CsA concentrations at 2 hours after dosing had the best value of correlation coefficient with the 12-h AUC. Abbreviated AUC could be calculated by stepwise multiple linear regression analysis and linear trapezoidal rule. The latter is more simple and superior to the former one.