Intern Med J, 47: 8. (2017)
Bakhtiar, M., Too, C., Tan, L., Sulaiman, S., Tang, M., Fauzi, N.-A., Nagum, A., Joseph, C., Kwok, F. and Rayappa, G.
Non-steroidal anti-inflammatory drugs (NSAIDs) hypersensitivity is one of the leading cause of adverse reactions and a matter of concern in susceptible patients, with NSAIDs induced urticaria/angioedema (NIUA) being the commonest phenotype. Positive associations between the human leukocyte antigen (HLA) and NSAIDs hypersensitivity have been observed in different populations.
The aims of this study were to determine the frequency of HLA genes in NIUA patients and NSAID-tolerant controls and, demonstrate the HLA associations of NIUA in a Malay population.
35 Malay patients with at least two chemically different NSAIDs hypersensitivity of the NIUA phenotype and 35 NSAIDs-tolerant controls following the 2013 European Network for Drug Allergy (ENDA) guideline for NSAIDs hypersensitivity were recruited. These subjects were genotyped for HLA-A, -B, -DRB1 and -DQB1 using polymerase chain reaction sequence-specific oligonucleotide probe hybridisation (PCR-SSO) method. A haplotype analysis was performed comparing the NIUA cases with 951 normal healthy controls.
The frequency of HLA-A*11:01 alleles was 27.1% in the NIUA group, compared with 8.6% in the NSAIDs tolerant group (odds ratio [OR] = 3.35, 95% confidence interval [CI] = 1.31–8.60, P < 0.05). The haplotype analysis revealed that HLA-A*11:01-B*15:02-DRB1*12:02-DQB1*03:01 and HLA-A*11:01-B*15:13-DRB1*12:02-DQB1*03:01 were significantly higher in NIUA (11.4% and 5.71% respectively) than in normal healthy controls (1.1%, OR = 11.76, 95% CI = 3.50–39.52, P = 0.001 and 0.21%, OR = 28.76, 95% CI = 3.93–210.48, P = 0.007 respectively).
These findings showed that HLA-A*11:01 was positively associated with NIUA in a Malay population. The haplotype findings also suggest that the HLA-A*11:01-B*15:02-DRB1*12:02-DQB1*03:01 and HLA-A*11:01-B*15:13-DRB1*12:02-DQB1*03:01 may be used as genetic markers to determine the NIUA phenotype in this population.