Pharmacogenomics最新文献

Aim: To investigate the association of DNA methylation, genetic polymorphisms and mRNA level of aminolevulinate synthase 1 (ALAS1) with antituberculosis drug-induced liver injury (AT-DILI) risk.Methods: Based on a 1:1 matched case-control study with 182 cases and 182 controls, one CpG island and three single nucleotide polymorphisms (SNPs) were detected. ALAS1 mRNA level was detected in 34 samples.Results: Patients with methylation status were at high risk of AT-DILI (odds ratio: 1.567, 95% CI: 1.015-2.421, p = 0.043) and SNP rs352169 was associated with AT-DILI risk (GA vs. GG, odds ratio: 1.770, 95% CI: 1.101-2.847, p = 0.019). ALAS1 mRNA level in the cases was significantly lower than that in the controls (0.75 ± 0.34 vs. 1.00 ± 0.42, p = 0.021).Conclusion: The methylation status and SNP rs352169 of ALAS1 were associated with AT-DILI risk.

Aim: To evaluate the association between irinotecan safety and the UGT1A1 gene polymorphism in colorectal cancer (CRC) patients.Materials & methods: The studies were systematically searched and identified from three databases (PubMed, Embase and The Cochrane Library) until 28 February 2023. The relationships were evaluated using pooled odds ratio (OR).Results: A total of 30 studies out of 600 were included, comprising 4471 patients. UGT1A1*28 was associated with a statistically significant increase in the OR for diarrhea (OR: 1.59, 95% CI = 1.24-2.06 in the additive model; OR = 3.24, 95% CI = 2.01-5.21 in the recessive model; and OR = 1.95, 95% CI = 1.42-2.69 in the dominant model) and neutropenia (OR = 1.70, 95% CI = 1.40-2.06 in the additive model; OR = 4.10, 95%CI = 2.69-6.23 in the recessive model; and OR = 1.93, 95% CI = 1.61-2.31 in the dominant model). Subgroup analysis indicated consistent associations in both Asian and non-Asian populations. UGT1A1*6 was associated with a statistically significant elevation in the OR for diarrhea (only in the recessive model, OR = 2.42; 95% CI = 1.14-5.11) and neutropenia (across all genetic models).Conclusion: The UGT1A1*28 and UGT1A1*6 alleles might be a crucial indicator for predicting irinotecan safety in CRC.

Aim: To explore the effect of CYP2D6*10 (100C > T) and ADRB1 1165 G > C polymorphisms on heart rate of post-PCI (percutaneous coronary intervention) patients treated with metoprolol succinate sustained-release tablets. Methods: A total of 756 inpatients with metoprolol succinate sustained-release tablets were selected and the genotypes of CYP2D6*10 and ADRB1 1165G > C were detected in 319 patients using gene chip detection. The target heart rate was defined as a resting heart rate < 70 beats/min. Clinical data were collected. Results: A total of 319 inpatients were enrolled in the study. The mutant allele frequencies of CYP2D6 and ADRB1 were 57.21 and 69.44%, respectively. Whatever the dose of metoprolol, the heart rates were lower in patients with homozygous mutation of CYP2D6 than those with heterozygous mutation and wild-type (p < 0.05). Nevertheless, this effect was not seen between different genotypes of ADRB1. Logistic regression analysis showed that the dose of metoprolol and the genotypes of CYP2D6 were predictors of heart rate <70 beats/min in these patients. Further multivariate analysis indicated that patients with homozygous mutation had better control of heart rates compared with those with wild-type and heterozygous mutation of CYP2D6*10 genotypes (all: p < 0.001). Conclusion:CYP2D6*10 polymorphisms were associated with the heart rate of post-PCI patients treated with metoprolol succinate sustained-release tablets.