Wu_2012_Zhonghua.Nei.Ke.Za.Zhi_51_524

OBJECTIVE: To study the relationship between the genetic polymorphisms of carboxylesterase 1 gene (CES1) and the susceptibility to antituberculosis drug-induced hepatotoxicity (ATBDIH). METHODS: Genetic polymorphisms of CES1 in 473 tuberculosis patients with or without hepatotoxicity (200:273) after antituberculosis chemotherapy were analyzed by PCR-MassArray. RESULTS: In 4 tags of CES1 single nucleotide polymorphism (SNP), the frequency of the rs1968753 allele had statistical difference between the hepatotoxicity group and the no-hepatotoxicity group(P = 0.0236). The characteristics of anti-hepatotoxicity had been shown relationship with rs8192950 (P = 0.044, OR = 0.649, 95%CI = 0.426 - 0.989, AC/AA) and rs1968753 (P = 0.048, OR = 0.556, 95%CI = 0.311 - 0.995, GG/AA). The diplotypes with 'CGC' haplotype exhibited significant protection against hepatotoxicity at one copy (P = 0.048, OR = 0.654, 95%CI = 0.430 - 0.996). CONCLUSIONS: The genetic polymorphisms of CES1 might have significant association with ATBDIH. SNP rs8192950 AC genotype and rs1968753 GG genotype might be the candidates for risk prediction of ATBDIH.