Table 4.
Pharmacogenetic HLA-associated drug hypersensitivity and related drug-induced syndromes. Adapted from Pavlos.54
| Syndrome and Drug | HLA Allele/genetic associations | Populations |
|---|---|---|
| SJS/TEN (SCAR) | ||
| Allopurinol | B*5801 (or B*58 haplotype) | Han Chinese, Thai, European, Italian, Korean98–103 |
| Carbamazepine | B*1502 | Han Chinese, Thai, Malaysian, Indian91,104–108 |
| B*1511 | Korean, Japanese86,109 | |
| B*1518, B*5901 and C*0704 | Japanese110 | |
| A*3101 | Japanese, northern European, Korean86–88 | |
| Oxcarbazepine | B*1502 and B*1518 | Han Chinese, Taiwanese90,111 |
| Lamotrigine | B*1502 | Han Chinese111 |
| B*38 | European102 | |
| Phenytoin | B*1502, B*1301, Cw*0801 and DRB1*1602 | Han Chinese92,111 |
| Sulfamethoxazole | B*38 | European102 |
| Methazolamide | B*5901, Cw*0102 alleles and B*5901–Cw*0102–A*2402 haplotype | Korean and Japanese112,113 |
| Sulphonamides | A*29, B*12 and DR7 | European112 |
| Oxicam | B*73, A*2 and B*12 | European102 |
|
| ||
| HSS/DIHS/DRESS | ||
| Abacavir | B*5701 | European, African80 |
| Allopurinol | B*5801 (or B*58 haplotype) | Han Chinese, Korean, Japanese, Thai, European99–101,103 |
| Nevirapine (hepatitis/low CD4+) | DRB1*0101 | Australian, European114,115 |
| DRB1*0102 | South African116 | |
| Nevirapine (DIHS/DRESS) | Cw*8 or CW*8–B*14 haplotype | Italian, Japanese117,118 |
| Cw*4 and DRB1*15 | Han Chinese119 | |
| B*3505 | Asian115 | |
| B*3501 and B*15/DRB1*15 | Australian57 | |
| Carbamazepine | 8.1 AH (HLA A*0101, Cw*0701, B*0801, DRB1*0301, DQA1*0501, DQB1*0201) | Caucasians 120 |
| A*3101 | Northern European, Korean and Japanese86–88 | |
| A*11 and B*51 (weak) | ||
|
| ||
| Delayed Rash (nonsystemic) | ||
| Efavirenz | DRB1*01 | French121 |
| Nevirapine | DRB1*01 | French 121 |
| Cw*04, B*3505; rs1576*G CCHCR1 status (GWAS) | African, Asian, European, Thai115,122–124 | |
| Aminopenicillins | A*2 and DR*52 | Italian125 |
| Carbamazepine (MPE) | A*3101 | Han Chinese, northern European88,126 |
| Oxcarbazepine-induced MPE | B*1502 | Han Chinese127 |
|
| ||
| Fixed Drug Eruption | ||
| Feprazone | B*22 | Italian37,128 |
| Sulfamethoxazole | A*30–B*13–Cw*6 haplotype | Turkish38 |
|
| ||
| DILI | ||
| Amoxicillin–clavulanate | DRB1*1501, DRB107 protective, A*0201, DQB1*0602 and rs3135388, a tag SNP of DRB1*1501–DQB1*0602 | European129–131 |
| Lumiracoxib | DRB1*1501–DQB1*0602–DRB5*0101– DQA1*0102 haplotype | International multicentre132 |
| Ximelagatran | DRB1*07 and DQA1*02 | Swedish133 |
| Diclofenac | ABCB11, C-24T, UGT2B7*2, IL-4 C-590-A | European134–136 |
| Isoniazid | NAT2 slow acetylator, CYP2E1*5 and *1B | European135,136 |
| Flucloxacillin | B*5701, DRB1*0107–DQB1*0103 | European137 |
| Lapatinib | DRB1*0701–DQA2*0201–DQB1*0202/0202 | International, multicentre138 |
| Ximelagatran | DRB1*07 and DQA1*02 | European133 |
DIHS: Drug-induced hypersensitivity syndrome, DILI: Drug-induced liver disease, DRESS: Drug reaction with eosinophilia and systemic symptoms, GWAS: Genome-wide association study, HSS: Hypersensitivity syndrome, MPE: Maculopapular eruption, SJS: Stevens–Johnson syndrome, TEN: Toxic epidermal necrolysis. SCAR: severe cutaneous adverse reaction, HLA human leukocyte antigen A, B, C, DRB1, DQA1, DQA2, DQB1 genes, CD4 (cluster of differentiation 4).