ABSTRACT
Background: The HLA-B*15:02 polymorphism in epileptic patients is known to be associated with carbamazepine-induced Stevens-Johnson syndrome (SJS). The prevalence of HLA-B*15:02 polymorphism seemed to be ethnic-specific with a higher frequency of HLA-B*15:02 in Asian compared to the Europeans. This study was performed to determine the frequency of the HLA-B*15:02 polymorphism in epileptic patients at the Chancellor Tuanku Muhriz Hospital-UKM Medical Centre (HCTM-UKMMC) using high resolution melting-real time PCR (HRM-QPCR) method. Methods: We performed a fast and effective in-house high resolution melting-real time polymerase chain reaction method and compared it with the conventional multiplex-PCR method. The specificity and sensitivity of each test were also determined using DNA from saliva. Results: Using the conventional multiplex-PCR approach for screening, 25 out of 64 (39.1%) epileptic patients were positive for HLA-B*15:02. However, using the HRM-QPCR technique, 24/64 (37.5%) of the patients were positive. The one patient who tested positive by the multiplex-PCR but negative using the HRM-QPCR turned out to be negative by DNA sequencing. The HRM-QPCR and DNA sequencing showed 100% sensitivity and specificity. The multiplex-PCR showed 100% sensitivity and 98.4% specificity compared to both HRM-QPCR and DNA sequencing. The HRM-QPCR is also more cost-effective (<$16.40 USD/test) and less time-consuming when compared to the multiplex-PCR ($25.15 USD/test).Conclusion: Our result suggested that multiplex PCR, HRM-QPCR and Sanger sequencing can be used for detection of HLA-B*15:02. However, a qualitative method such as multiplex PCR should be confirmed with other quantitative methods such as HRM-QPCR and Sanger sequencing.
ABSTRACT
Background & Objective: Association between HLA-B*1502 and carbamazepine-induced StevenJohnson syndrome/toxic epidermal necrolysis (CBZ-SJS/TEN) was reported in many Southeast Asian populations but not in Indonesian. The purpose of this study was to evaluate the association between HLA-B*1502 andCBZ-SJS/TEN in an Indonesian population. Methods: Patients with history of CBZ-SJS/TEN are recruited as cases and those who tolerated CBZ as controls. HLA-B typing was performed. Results: We recruited 14 cases with CBZ-SJS/TEN and 53 controls. Positive HLA-B*1502 was found in 8 (57.1%) cases and 14 (26.4%) controls (OR 3.7, 95% CI 1.09-12.61, p=0.035). Conclusion: HLA-B*1502 is associated with CBZ-SJS/TEN patients in Indonesian.