0%, 45.6%, and 20.4%, respectively, and GPX1; 67.0%, 31.1%, and 1.9%, respectively) and the larger control group matched for sex and age. Genotype distribution of SOD2 and GPX1 in the main pharmacological drug groups

related to DILI is outlined in Table 2. Subjects with an SOD2 Ala allele (Val/Ala or Ala/Ala genotype) had a higher risk of DILI than those with the SOD2 Val/Val genotype, both in overall drugs studied (n = 185; OR = 1.7 [1.1-2.6], Pc = 0.048) and in the CNS drugs category (n = 28; OR = 3.8 [1.1-13.0], P = 0.029/Pc = 0.058). When the analysis of the SOD2 polymorphism was restricted to patients with cholestatic/mixed liver injury, the SOD2 C allele frequency was higher among patients receiving NSAIDs (n = 12; OR = 2.2 [1.2-3.8], Pc = 0.017) and CNS drugs

(n = 12; OR = 3.1 [1.7-5.6], Pc = 0.0003). Z-VAD-FMK research buy Whereas the GPX1 T (Leu) allele was more frequently found in DILI patients induced by anti-infective drugs (n = 35; OR = 2.6 [1.3-4.9], Pc = 0.011). On the genotype level, the frequency of overall DILI patients carrying the GPX1 TC and TT genotypes was higher than that in the control subjects (n = 185; OR = 1.5 [1.0-2.2], P = 0.042/Pc = 0.084) and in the group receiving anti-infective drugs (n = 59; OR = 2.3 [1.3-4.1], Pc = 0.0098). To justify the use of the larger non–drug-matched TSA HDAC cost control group, analyses were also undertaken using smaller drug-matched control groups. An association between the SOD2 C allele and cholestatic/mixed type of liver injury induced by NSAIDs was found when using the drug-matched control group (OR = 2.6 [1.4-4.5], Pc = 0.0028). In addition, no association was found between the SOD2 C allele and cholestatic/mixed type of liver injury induced by amoxicillin-clavulanate when compared with drug-matched controls, reflecting the results obtained with the larger sex- and age-matched control group. Moreover, the GPX1 allele frequency in NSAID-matched and amoxicillin-clavulanate–matched

controls corresponded to those of the larger sex- and age-matched control group (Supporting Information Table 1). The SOD2 Ala/Ala genotype distribution in DILI Urocanase patients classified by the formation of reactive intermediates and according to the type of liver injury is outlined in Table 3. Patients with cholestatic/mixed type of DILI induced by quinones, quinone-like intermediates (quinone methides and quinone imines), or epoxides (n = 58) were found to be more prone to contain the SOD2 Ala/Ala genotype when compared with healthy controls (OR = 3.0 [1.7-5.5], Pc = 0.0008). Similarly, a positive association between the SOD2 Ala/Ala genotype and the risk of cholestatic/mixed type of DILI from drugs forming S-oxides, diazenes, nitroanion radicals, and iminium ions (n = 5) was observed (OR = 16.0 [1.8-146.1], Pc = 0.009).