1.Study on the Correlation of Gene Polymorphism with Antiplatelet Efficacy of Clopidogrel in PAD Patients
Xiaoyu XU ; Yang LIN ; Xiujin SHI ; Xiqiao XU
China Pharmacy 2017;28(26):3604-3609
OBJECTIVE:To investigate the correlation of gene polymorphism in peripheral artery disease(PAD)patients with antiplatelet efficacy of clopidogrel. METHODS:Reviewing related domestic and foreign literatures in recent years,the correlation of gene polymorphism in PAD patients with antiplatelet efficacy of clopidogrel was summarized and analyzed. RESULTS&CON-CLUSIONS:At present,a variety of genes associated with clopidogrel antiplatelet efficacy and major adverse cardiovascular events (MACE)have been identified,including cytochrome P450(CYP)2C19,adenosine three phosphate binding cassette B subfamily 1 (ABCB1),paraoxonase 1 (PON1) and adenosine diphosphate P2Y12 receptor (P2Y12),etc. CYP2C19*2,*3 allele may reduce the antiplatelet effect of clopidogrel. Their correlation has been confirmed by a number of studies,and study results are broadly con-sistent. Mutations in the ABCB1 C3435T and PON1 Q192R sites may lead to a lower response to clopidogrel and increase the risk of MACE;but there is a lack of large-scale prospective clinical studies,and the present results are inconsistent. P2Y12 gene poly-morphism in PAD patients has not been found to be significantly associated with clopidogrel efficacy.
2.Safety comparison of high-dose methotrexate via different intravenous infusion devices in pediatric patients with malignant brain tumors
Xiqiao XU ; Zhengyuan SHI ; Chunjing YANG ; Shumei WANG
China Pharmacy 2023;34(7):844-848
OBJECTIVE To compare the safety of high-dose methotrexate (HD-MTX) via peripherally inserted central catheter (PICC) and totally implantable venous access port (TIVAP) in pediatric patients with malignant brain tumors. METHODS Patients with malignant brain tumors who received HD-MTX via PICCs or TIVAPs in our hospital from July 2018 to April 2022 were retrospectively analyzed. Clinical data were collected to compare differences in blood concentration of methotrexate (MTX),the incidence of adverse events (including adverse drug reactions and catheter-related complications) and length of stay in hospital. Multivariate linear regression was applied to analyze the factors that influenced the blood concentration of MTX. RESULTS A total of 107 patients were included in the study,with 65 patients in the PICC group and 42 patients in the TIVAP group. Blood concentration of MTX at 24 h (C24 h) in TIVAP group was significantly higher than PICC group ([ 126.87±61.99) μmol/L vs. (102.45±48.77) μmol/L,P<0.05). There was no significant difference in blood concentration of MTX at 42 h (C42 h),compared with PICC group (P>0.05). Results of multivariate linear regression analysis showed that TIVAP was associated with the increase of C24 h(P<0.05). No significant differences were observed in the incidence of adverse events and the length of stay in the hospital between 2 groups (P>0.05). CONCLUSIONS Risk of adverse events is not increased,although the MTX C24 h level is elevated after administration of TIVAP. TIVAP is a safe choice for HD-MTX therapy with implementing therapeutic drug monitoring.
3.Associations of MTRR gene polymorphism and methotrexate plasma concentration and adverse drug reaction in children with intracranial tumors
Danqi ZHAO ; Miao LI ; Zhengyuan SHI ; Xiqiao XU ; Shumei WANG
China Pharmacy 2024;35(21):2646-2651
OBJECTIVE To investigate the impact of the methionine synthase reductase (MTRR) rs10380 C>T gene polymorphism on methotrexate (MTX) plasma concentration, adverse drug reaction, and prognosis in children with intracranial tumors. METHODS Peripheral blood was collected from children with intracranial tumors, and genomic DNA was extracted. The MTRR rs10380 C>T genotype was analyzed using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. The association of the MTRR rs10380 C>T gene polymorphism with the ratio of MTX plasma concentration to dose (C/D ratio), adverse drug reaction, tumor recurrence, and metastasis was analyzed. Bioinformatics analysis was used to explore the association of the rs10380 genotype and MTRR gene expression and its possible mechanisms. RESULTS A total of 75 children were included in the study. The distribution frequencies of the wild-type CC genotype and C allele of rs10380 were 62.67% and 81.33%, respectively, while the distribution frequencies of the variant CT genotype and T allele were 37.33% and 18.67%, respectively, which were in accordance with Hardy-Weinberg equilibrium(P>0.05). The incidence of electrolyte disorders (51.06%) and tumor metastasis rate (57.45%) in children with the CC genotype were significantly higher than those with the CT genotype (P<0.05). No significant differences were observed in the 24-hour and 42-hour C/D ratios and recurrence rates between the two genotypes of children (P>0.05). Bioinformatics analysis showed that MTRR protein mainly works in conjunction with 10 proteins, including MMAA, and was involved in various biological processes such as sulfur amino acid biosynthesis. CONCLUSIONS The MTRR rs10380 CC genotype may be a risk factor for electrolyte disorders and tumor metastasis in children with intracranial tumors after MTX chemotherapy.