Aggregated risk of carbamazepine (CBZ)‐induced cutaneous adverse drug reactions (cADRs) with different HLA variants are unclear and limited in terms of the power of studies . This study aimed to assess the aggregated risk of CBZ‐induced cADRs associated with carrying the following HLA variants: HLA‐B*15:02 , HLA‐B*15:11 , HLA‐B*15:21 , HLA‐B*38:02 , HLA‐B*40:01 , HLA‐B*46:01 , HLA‐B*58:01 , HLA‐A*24:02 , and HLA‐A*31:01 . Literature was searched in different databases following PRISMA guidelines. The outcomes were measured as odds ratio (OR) using RevMan software by a random/fixed effects model, where p < 0.05 was set as statistical significance. In total, 46 case–control studies met the inclusion criteria and were included in this analysis consisting of 1817 cases and 6614 controls. It was found that case‐patients who carried the HLA‐B*15:02 allele were associated with a significantly increased risk of CBZ‐induced Stevens−Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) compared to controls (OR 26.01; 95% CI 15.88–42.60; p < 0.00001). The aggregated risk of cADRs was slightly higher in Asian compared to Caucasian patients (Asians: OR 14.84; 95% CI 8.95–24.61; p < 0.00001; Caucasians: OR 11.65; 95% CI 1.68–80.70; p = 0.01). Further, HLA‐B*15:11 , HLA‐B*15:21 , or HLA‐A*31:01 allele was also associated with significantly increased risk of CBZ‐induced cADRs ( HLA‐B*15:11: OR 6.08; 95% CI 2.28–16.23; p = 0.0003; HLA‐B*15:21: OR 5.37; 95% CI 2.02–14.28; p = 0.0008; HLA‐A*31:01: OR 5.92; 95% CI 4.35–8.05; p < 0.00001). Other HLA variants were not found to have any significant associations with CBZ‐induced cADRs. Strong associations between the HLA‐B*15:02 , HLA‐B*15:11 , HLA‐B*15:21 , or HLA‐A*31:01 allele with CBZ‐induced cADRs have been established in this analysis. Pharmacogenetic testing of particular HLA alleles before initiation of CBZ therapy may be beneficial to patients and may help to eradicate cADRs substantially.

Busulfan is widely used as a chemotherapy treatment before hematopoietic stem-cell transplantation (HSCT). However, the response of busulfan is highly variable and unpredictable, whereby the pharmacogenetic interference of glutathione S-transferase (GST) has strong evidence in Caucasians and some adult Asians but not in pediatric Asian patients. This study was aimed at investigating the associations of GST genetic polymorphisms with variations in the pharmacokinetic (PK) properties of busulfan in pediatric Asian patients. This retrospective cohort study recruited 92 pediatric patients. The polymorphism of GSTA1 was genotyped by Sanger sequencing, and GSTM1 and GSTP1 were genotyped by real-time PCR. Drug concentration and PK estimation were identified using an LC-MS/MS method and a noncompartmental model. Statistical analysis was performed by R software. Out of 92 patients, 48 (53%) were males, the mean age was 8.4 ± 5.12 years old, and the average weight was 26.52 ± 14.75 kg. The allele frequencies of GSTA1*B and of GSTM1 and GSTP1* deletions were 16.9%, 68.5%, and 21.2%, respectively. Patients with GSTA1*B had a statistically significant impact on the PK of busulfan, whereas those with GSTM1 and GSTP1 did not (p > 0.05). The carriers of GSTA1*B showed a significant difference compared to noncarriers in terms of t1/2 (for first dose: 161.9 vs. 134.3 min, p = 0.0016; for second dose: 156.1 vs. 129.8, p = 0.012), CL (88.74 vs. 124.23 mL/min, p = 0.0089), Cmax (4232.6 vs. 3675.5 ng/mL, p = 0.0021), and AUC (5310.6 vs. 4177.1 µM/min, p = 0.00033). The augmentation of AUC was around 27.1% in patients carrying the GSTA1*B variant. The GSTA1 polymorphism was significantly associated with variations of the pharmacokinetic properties of busulfan treatment in pediatric Asian patients.

Background: The relationship between HLA-B*15:02 and Severe Cutaneous Adverse Reactions was rigorously examined in Japanese, Han Chinese, Thais, and Caucasians. However, the number of studies about this topic in Vietnamese population is still limited and mostly focuses on the North of Vietnam.Objective: This study aims to clarify the genetic culprit of SCARs in Vietnamese population, particularly in the South of Vietnam, and to validate our result by a meta-analysis about this topic in Vietnamese.Method: A retrospective case-control study with 37 patients treated with carbamazepine monotherapy. Statistical calculation and meta-analysis were performed by R software.Result:HLA-B*15:02 increases the risk of SJS 12.5 times higher in CBZ-treated patients (p-value = 0.017). However, this allele has no impact on MCARs (Mild Cutaneous Adverse Reactions) of CBZ. The number needed to test and the number needed to genotype is two and nine patients respectively.Conclusion: This study recommends more investigations about the cost-effectiveness of this test to accelerate the protection of Southern Vietnamese from SCARs.