There are many studies that investigate genetic factors that cause predisposition to drug hypersensitivity. However, most studies have focused on specific phenotypes or drugs. Thus, we planned to perform a genome-wide association (GWAS) study to discover the common genetic markers associated with both in immediate and delayed drug hypersensitivity reactions.
We studied 190 patients who were diagnosed with drug hypersensitivity at a tertiary referral hospital and 133 control subjects. We divided the patients into 2 groups; immediate-type hypersensitivity reaction (n=109) and delayed-type hypersensitivity reaction (n=81), according to the type of drug hypersensitivity. Genome-wide SNP genotyping of the patients was performed using genomic DNA from peripheral blood lymphocytes.
In the immediate-type hypersensitivity reaction group, we found signification associations with a total of 11 genes, whereas five genes showed signification association in the delayed-type hypersensitivity reaction group. The top 5 SNPs were rs17732181, rs12674658, rs10463158, rs10028040, and rs1330221 in the immediate-type hypersensitivity groups. As well, rs10028040, rs17732181, rs10463158, rs28786672, and rs12674658 have also been identified in the delayed-type hypersensitivity groups. Interestingly, there were two genes that overlapped in the two groups, namely, the Lipopolysaccharide-Responsive Beige-like Anchor (LRBA) gene and the Methionine adenosyltransferase 2 beta (MAT2B) gene. Associations with the SNPs of these genes were commonly found in both immediate and delayed type hypersensitivity reactions (rs10028040 of LRBA, P = 5.63 x 10-14, P = 7.19 x 10-12 respectively, and rs10463158 of MAT2B, P = 6.40 x 10-12, P = 5.25 x 10-12respectively).
Genetic variants of the LRBA and the MAT2B genes might be significant genetic markers of drug hypersensitivity reactions. Replication studies are also needed to confirm our findings.