Oxcarbazepine (OXC) is one of the preferred drugs for partial seizures and generalized tonic-clonic seizures. However, clinical studies have found that there are considerable differences among different populations in OXC therapeutic efficacy or safety that result from the function changes of metabolic enzymes, transporters and other receptors involved in pharmacokinetics and pharmacodynamics in vivo. The authors collected all the information on the clinically reported associations between variants of common genes (e.g., UGT1A9, HLA-B, ABCB1) and OXC. In conclusion, these associations based on variants are beneficial for adjusting the medication regimen, which could be useful for individualized treatment with OXC.

Background: 6-mercaptopurine usage is associated with myelotoxicity and increased risk in patients carrying metabolism-related genetic variations. This study aimed to determine the frequency of candidate gene polymorphisms and their association with 6-mercaptopurine intolerance. Methods: A total of 41 patients on acute lymphoblastic leukaemia treatment were genotyped for TPMT and NUDT15 (rs116855232) alleles, and their association with dose intensity was analyzed. Results: The defective TPMT*3C allele frequency was 9.8%. The median maintenance dose intensity for TPMT*1/*3C participants was considerably lower (47%) when compared with the TPMT*1/*1 wild-type (77%), although not statistically significant. Conclusion: This is the first pharmacogenetics study carried out in a black Zimbabwean leukemia patient cohort. The high defective TPMT*3C (9.8%) allele frequency points to the potential utility of pharmacogenetics testing for safe usage of 6-mercaptopurine in this population.

Background: The effect of multiple mutations in CYP2C19, PON1 and ABCB1 genes on the effectiveness and safety of dual antiplatelet therapy after percutaneous coronary intervention remains unclear. Methods: In total, 263 Chinese Han patients were enrolled in this study. Platelet aggregation rates and thrombosis risk were used to compare clopidogrel responses and outcomes in patients with different numbers of genetic mutations. Results: Our study demonstrated that 74% of the patients carried more than two genetic mutations. High platelet aggregation rates were associated with genetic mutations in patients receiving clopidogrel and aspirin after percutaneous coronary intervention. Genetic mutations were closely related to the recurrence of thrombotic events, but not bleeding. The number of genes that become dysfunctional in patients is directly correlated with the risk of recurrent thrombosis. Conclusion: Compared with CYP2C19 alone or the platelet aggregation rate, it is more helpful to predict clinical outcomes by considering the polymorphisms of all three genes.

Aim: We previously conducted exome-wide association study in acute lymphoblastic leukemia patients and identified association of five SNPs with asparaginase-related thrombosis. Here we aimed to replicate these findings in an independent patient cohort and through analyses in vitro. Patients & methods: SNPs located in IL16, MYBBP1A, PKD2L1, RIN3 and MPEG1 genes were analyzed in patients receiving Dana-Farber Cancer Institute acute lymphoblastic leukemia treatment protocols 05-001 and 11-001. Thrombophilia-related variations were also analysed. Results: IL16 rs11556218 conferred higher risk of thrombosis and higher in vitro sensitivity to asparaginase. The association was modulated by the treatment protocol, risk group and immunophenotype. A crosstalk between factor V Leiden, non-O blood groups and higher risk of thrombosis was also seen. Conclusion: IL16 and factor V Leiden variations are implicated in asparaginase-related thrombosis.

Aim: The frequencies of SLCO1B1*5 and CYP2C9*2 and *3 in specific Asian, Native Hawaiian and Pacific Islander (NHPI) subgroups are unknown. Patients & methods: Repository DNA samples from 1064 women self-identifying as Filipino, Korean, Japanese, Native Hawaiian, Marshallese or Samoan and aged 18 years or older were used for targeted sequencing of three genetic variants (rs4149056, rs1799853 and rs1057910). Results: SLCO1B1*5 was significantly less frequent in NHPI women (0.5-6%) than in Europeans (16%). Except for Koreans, CYP2C9*2 (0-1.4%) and *3 (0.5-3%) were significantly less frequent in all subgroups than in Europeans (8 and 12.7%, respectively). Prior reports showed that Asian and NHPI individuals have significantly higher ABCG2 Q141K allele frequency (13-46%) than Europeans (9.4%). Combined phenotype rates for rosuvastatin and fluvastatin revealed that Filipinos and Koreans had the highest frequencies of statin-associated myopathy symptoms risk alleles. Conclusion: Differences in ABCG2, SLCO1B1 and CYP2C9 allele frequencies among different racial and ethnic subgroups highlight the need for increased diversity in pharmacogenetic research. Risk alleles for statin-associated myopathy symptoms are more prevalent in Filipinos, underscoring the importance of genotype-based statin dosing.