555 Association of aromatic antiepileptic drugs induced severe cutaneous adverse reactions and HLA allele or a new susceptibility gene, CGREF1

Abstract

Background: Aromatic antiepileptic drugs (AEDs) induced Severe cutaneous adverse reactions (SCARs) refers to a group of life-threatening severe drug eruptions characterized by the skin and mucous membrane involvement. The pathogenesis is unclear; it is considered that genetic susceptibility and innate immune response together contributed to it. Our aim is to identify the susceptibility loci for AEDs-related SCARs to provide the basis and proof for individualized and accurate medical care and genetic biomarkers for screening and prevention of AEDs-related SCARs. Objective: To investigate the correlation between HLA-A, B, C and aromatic antiepileptic drugs induced-severe drug eruption in Han Chinese populations, and other candidate susceptibility genes. Material and Methods: Using high resolution Sequencing-based typing (SBT) techniques, we analyzed the genotypes of HLA-A,B,C of 12 cases of aromatic anti-epileptic drugs (AEDs) induced SCARs and whole-exome sequencing and correlation analysis were performed on 6 patients suffering from AEDs-SCARs with specific HLA alleles to explore possible candidate susceptibility genes. Results: The allele frequencies of HLA-A*03:01 (8.33% vs 0.79%,OR=11.465, P<0.05), HLA-B*13:01 (25% vs 7.78%, OR=3.951, P<0.05 ), HLA-B*52:01 (8.33% vs 0.61%, OR=14.766, P<0.05) were significantly higher in the patients with AEDs-SCARs than in the healthy controls; Initially CGREF1(NM_006569) gene was locked, which may be associated with the pathogenesis of AEDs-SCARs. However, due to the limited number of samples, it is necessary to expand the sample size for further verifications. Conclusions: In Han Chinese population, we studied the correlations between HLA alleles and AEDs-SCARs, and we found that allele frequencies of the three HLA alleles, HLA-A*03:01, -B*13:01, and -B*52:01 was significantly higher than that of the healthy controls; CGREF1 gene may be related to AEDs-SCARs.