HLA-B and HLA-C loci genetic polymorphism as a marker of severe cutaneous adverse reactions in Thai patients on allopurinol

Abstract

There were two main purposes in this present study; first, to investigate the causative drugs, the prevalence and mortality rates related to severe cutaneous adverse reactions (SCAR) during 2003-2007 using retrospective data collected from electronic database of Adverse Drug Reaction Monitoring Center and Siriraj Computer Center, Siriraj Hospital, Bangkok; second, to determine the association between HLA-B[superscript *]5801 and HLA-Cw[superscript *]0302 alleles to SCAR induced by allopurinol in Thai patients using case-control study. There were 25 case patients who experienced allopurinol induced SCAR, 9 case patients who experienced other cutaneous adverse reaction from allopurinol and 48 allopurinol tolerant controls participate in the study. SCAR was found in 136 patients. The prevalence of SJS, TEN and HSS were most often found in patients treated with carbamazepine (3.26 per 1,000 patients), allopurinol (0.21 per 1,000 patients) and phenytoin (2.64 per 1,000 patient), respectively. Mortality rates of SJS, TEN and HSS were 6.90%, 50.0% and 12.82% respectively. Allopurinol revealed the highest mortality rate. HLA-B[superscript *]5801 and HLA-Cw[superscript *]0302 alleles were found in all 25 cases (100%) of patient with SCAR, only 7 controls (14.58%) of allopurinol tolerant patients have HLA-B*5801 and HLA-Cw[superscript *]0302 alleles. Risk of SCAR in patients with HLA-B*5801 and HLA-Cw[superscript *]0302 alleles was 282 times higher (95%CI 15.45 to 5153.83, P-value < 0.001). This study was the first that reported the presence of HLA-B[superscript *]5801 and HLA-Cw[superscript *]0302 alleles in all patients who experienced exfoliative dermatitis from allopurinol. Model to predict the adverse drug reactions from allopurinol using logistic regression demonstrated its association to three main factors; HLA-B[superscript *]5801 allele, female gender and underlying of diabetes mellitus.