Relationship between eNOS 894G>T Polymorphism and the Antihypertensive Efficiency of Two Dihydropyridine Calcium Channel Blocker Drugs, Azelnidipine and Nitrendipine, in Chinese EH Patients
Zhiying Luo,
Fazhong He,
Jianquan Luo,
Wei Zhang
Issue:
Volume 3, Issue 1-4, January 2015
Pages:
1-6
Received:
23 October 2014
Accepted:
25 October 2014
Published:
24 November 2014
Abstract: Background: Dihydropyridine calcium-channel blockers (dCCBs) were widely used in anithypertensive treatment. The aim of this study was to examine the effect of polymorphisms of CACNA1C, eNOS and RGS2 on the antihypertensive efficiency of dihydropyridine calcium channel blocks (dCCBs) in Chinese patients with essential hypertension (EH). Methods: A total of 107 untreated Chinese mild to moderate EH patients were enrolled in this study, and had been prescribed azelnidipine or nitrendipine as monotherapy. All patients who had gave informed consent for genetic research were divided into two groups: treated with azelnidipine or nitrendipine for at leaset 6 weeks. Five polymorphisms of three blood pressure (BP) and hypertension susceptible genes were studied in our research, and these polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Every patients’ BP and heart rate were measured at 0 week, 2 weeks, 4 weeks and 6 weeks. The biochemical parameters of blood were detected before and 6 weeks after the administration. Adverse effects were evaluated at the last visitation. Results: Both the systolic and diastolic BP levels were significanlty decreased after six weeks of dCCBs treatment, from 149.3 ± 9.2 mmHg to 132.2 ± 11.7 mmHg and form 97.9 ± 3.0 mmHg to 85.5 ± 7.5 mmHg, as well as the levels of TP, TBIL, CHO and LDL, the P-values were P=0.017, P=0.045, P=0.039, P=0.041 respectivley. As 11 of 75 patients appeared adverse reactions, the rate of adverse effects showed no difference in various genotypes. There were significant interactions between eNOS G894T polymorphism and △DBP, △MBP on azelnidipine therapy patients, but not in nitrendipine, the GG genotype carriers were more sensitive in blood decrease than GT/TT genotype carriers (P<0.05). Conclusion: CCBs had potential hepatoprotective and antiatheroscloresis effects for Chinese EH paitents. And the eNOS G894T polymorphism is associated with the hypotensive effect of azelnidipine.
Abstract: Background: Dihydropyridine calcium-channel blockers (dCCBs) were widely used in anithypertensive treatment. The aim of this study was to examine the effect of polymorphisms of CACNA1C, eNOS and RGS2 on the antihypertensive efficiency of dihydropyridine calcium channel blocks (dCCBs) in Chinese patients with essential hypertension (EH). Methods: A ...
Show More
Moderate Effect of GGCX Polymorphisms on Patients Warfarin Dosage Requirement- A Meta-Analysis
Zhiying Luo,
Xi Li,
Mouze Liu,
Yan Shu,
Jiye Yin,
Xiaoping Chen,
Jianquan Luo,
Xiaobing Li,
Wei Zhang
Issue:
Volume 3, Issue 1-4, January 2015
Pages:
7-13
Received:
19 November 2014
Accepted:
22 November 2014
Published:
27 December 2014
Abstract: Objective: Association studies on the effects of GGCX gene polymorphisms on warfarin stable dose have shown conflicting results. The aim of this study is to quantitatively summarize whether GGCX gene polymorphisms have potential roles in warfarin dose requirement. Methods: Publications were searched in PubMed, Medline and ISI Web of Knowledge and chosen by exact inclusion and exclusion criteria. A meta-analysis was conducted by using Revman 5.0 software to determine the association between common polymorphisms of the three genes and warfarin dose requirement. Results: Data were extracted from 13 publications with 4167 patients enrolled. Two common polymorphisms (rs699664, rs12714145) of GGCX were included for further meta-analyses. Comparing to rs699664AA geontype carriers, rs699664GG genotype carriers requered higer 3% [95% CI: 2% - 4%, P-valus < 0.0001] warfarin dose. The warfarin dosage requirement showed no significant difference between rs699664GG and rs699664GA genotype carriers, P=0.51. Compared to rs12714145AA carriers, the GG and GA genotype carriers needed 5% (95% CI, 1% - 9%; P = 0.01) and 4% (95% CI, 1% - 8%; P = 0.02) lower warfarin dosage, respectively. The warfarin dosage requirement showed no significant difference between GG and GA genotype carriers, P=0.12. Conclusion: Our study showed that GGCX polymorphisms were significantly associated with warfarin dose requirement. These polymorphisms should be considered in future warfarin personalized treatment.
Abstract: Objective: Association studies on the effects of GGCX gene polymorphisms on warfarin stable dose have shown conflicting results. The aim of this study is to quantitatively summarize whether GGCX gene polymorphisms have potential roles in warfarin dose requirement. Methods: Publications were searched in PubMed, Medline and ISI Web of Knowledge and c...
Show More
Gender, but Not CYP2C19 Genotypes and CYP3A Phenotypes, is a Major Determinant of Ilaprazole Pharmacokinetic
Shan Cao,
Gan Zhou,
Yao Chen,
Dong Guo,
Zhi-rong Tan,
Lan Fan,
Hai-tang Hu,
Xiang-hong Qin,
Hong-hao Zhou,
Dong-sheng Ouyang,
Wei Zhang
Issue:
Volume 3, Issue 1-4, January 2015
Pages:
14-20
Received:
16 September 2014
Accepted:
24 November 2014
Published:
27 January 2015
Abstract: The purpose of the study was to assess the impact of CYP2C19 genotypes, CYP3A phenotypes and gender-related difference on the pharmacokinetics of new proton pump inhibitor ilaprazole. Twenty-four healthy Chinese volunteers (age 24.0 1.9 years) were enrolled in an open-label study stratified for gender (12 males and 12 females) and their CYP2C19 genotype (12 of CYP2C19*1/*1 and 12 of CYP2C19*1/*2 or *1/*3). After a single 10-mg dose of ilaprazole was administrated, blood samples were collected at time 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36h from all subjects. Ilaprazole and its metabolite sulfone-ilaprazole plasma concentrations were measured using the well-validated HPLC/MS/MS method. CYP3A phenotype was determined by the classic CYP3A probe drug midazolam one week after the clinical trial. The kinetics characteristics of ilaprazole and sulfone-ilaprazole were significantly influenced by gender. The clearance/systemic bioavailability (CL/F) of ilaprazole was much lower in female than in male (2.5 1.0 versus 3.7 1.6 h-1, P = 0.029), difference became more significant even after corrected by body weight (P = 0.008). However, the differences on half-life, AUC0-36 and AUC0→∞ of ilaprazole between genders were not significantly after normalized by body weight. As for sulfone ilaprazole, larger AUC0→36 and AUC0→∞ were detected in female when compared with male (406.8 126.3 vs. 246.7 70.0 ng • h/ml, P = 0.007, and 606.7 224.5 vs. 332.0 117.1 ng • h/ml, P = 0.001), discrepancies were still significant after corrected by total body weight, P value were 0.017 and 0.010 respectively. The pharmacokinetics parameters of ilaprazole and ilaprazole sulfone were neither different across CYP2C19 genotype groups nor related to CYP3A phenotype. CL/F of ilaprazole were much smaller in women than in men even after adjusted by body weight, indicating great effect of gender on the pharmacokinetics of ilaprazole. CYP2C19 genotypes and CYP3A phenotypes did not affect the pharmacokinetics of ilaprazole or sulfone-ilaprazole.
Abstract: The purpose of the study was to assess the impact of CYP2C19 genotypes, CYP3A phenotypes and gender-related difference on the pharmacokinetics of new proton pump inhibitor ilaprazole. Twenty-four healthy Chinese volunteers (age 24.0 1.9 years) were enrolled in an open-label study stratified for gender (12 males and 12 females) and their CYP2C19 g...
Show More
