Association of ABCB1 , CYP3A4 , EPHX1 , FAS , SCN1A , MICA, and BAG6 polymorphisms with the risk of carbamazepine‐induced S tevens‐ J ohnson syndrome/toxic epidermal necrolysis in C hinese H an patients with epilepsy

Summary Objective This study explored the association between the risk of carbamazepine ( CBZ )–induced S tevens‐ J ohnson syndrome ( SJS )/toxic epidermal necrolysis ( TEN ) and CBZ dose, dose‐adjusted concentration, and ABCB1 ,   CYP3A4 ,   EPHX1 ,   FAS ,   SCN1A ,   MICA, and   BAG6 polymorphisms in patients of H an ethnicity with epilepsy who were living in northeastern C hina. Materials and methods We determined the genotypes of patients with CBZ ‐ SJS / TEN and CBZ ‐tolerant patients, who were used as controls, for ABCB1 ,   CYP3A4 ,   EPHX1 ,   FAS ,   SCN1A ,   MICA, and   BAG6 polymorphisms by polymerase chain reaction ( PCR) amplification and direct sequencing. We measured the steady‐state serum CBZ concentrations using fluorescence polarization immunoassay for the control patients. Results We observed statistically significant differences in EPHX1 c.337T>C polymorphisms between patients with CBZ ‐ SJS / TEN and CBZ ‐tolerant controls in terms of allelic and genotypic frequencies (p =   0.011 and p =   0.007, respectively). The C allele and the C ‐ G diplotype of EPHX1 may play important roles in increasing the risk of CBZ ‐ SJS / TEN development (odds ratio [ OR]  0.478, 95% confidence interval [ CI]  = 0.267–0.855, p =   0.011; OR  = 0.213, 95% CI  = 0.049–0.930, p = 0.025, respectively). We did not observe any significant associations between ABCB1 ,   CYP3A4 ,   EPHX1 ,   FAS ,   SCN1A ,   MICA or   BAG6 genes and CBZ dose or dose‐adjusted concentration in CBZ ‐tolerant patients. Significance We found a significant association between EPHX1 c.337T>C polymorphisms and the development of CBZ – SJS / TEN in patients of Han ethnicity living in northeastern China. EPHX1 c.337T>C polymorphisms may contribute to the risk of severe CBZ ‐ SJS / TEN by increasing the concentration of a CBZ metabolite, CBZ ‐10,11‐epoxide, in patients with epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .