Hepatic Adverse Effects and Genetic Polymorphisms of NAT2 and CYP2C9

Abstract

Cotrimoxazole also known as sulfamethoxazole-trimethoprim (SMX-TMP) is a well-established antibiotic combination in clinical medicine. Post metabolism by N-acetyltransferase (NAT) and Cytochrome P450 2C9 (CYP2C9), SMX is bio-transformed into non-toxic and/or toxic intermediates. The pharmacogenetic associations between the variants of these genes and liver injury caused by SMX-TMP are still a mystery. Huang and colleagues studied the Han Chinese diabetes patients living in Taiwan and investigated their susceptibility to SMX-TMP induced Liver injury (SILI) and polymorphisms in the genes of both NAT and CYP2C9 enzymes. There were 145 controls and 158 SILI patients recruited for this investigation. CYP2C9 rs1799853, rs1057910, and rs4918758, NAT2 rs1495741, rs1041983, rs1801280, and other major genetic variants of these enzymes were assayed. NAT2 rs1495741 variant AA genotype and rs1041983 variant TT were present at a higher frequency in the SILI group as compared to the control group. Slow acetylators were greater in the SILI as compared to the control (43.7 vs. 25.5%; P = 0.001). CYP2C9 variants, interestingly, did not show any significant difference between the control and SILI cohorts. Individuals that were NAT2 slow acetylators were at a greater risk of SILI, post adjustment of confounding factors, particularly those that had mixed type and hepatocellular SILI. Their study concluded that CYP2C9 genetic polymorphisms are not associated with SILI susceptibility whereas NAT2 slow acetylators are at an increased risk of SILI in the Han Chinese population. Pharmacogenet Genomics. 2021 Dec 1;31(9):200-206.