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中华诊断学电子杂志 ›› 2017, Vol. 05 ›› Issue (04) : 230 -234. doi: 10.3877/cma.j.issn.2095-655X.2017.04.004

所属专题: 文献

心脑血管疾病诊治

新疆哈萨克族、维吾尔族高血压患者细胞色素P450 3A5基因多态性与氨氯地平预期降压疗效的关系
张荣秀1, 谷兰平1, 周晓欢1, 徐新娟1,()   
  1. 1. 830054 乌鲁木齐,新疆医科大学第一附属医院高血压科
  • 收稿日期:2017-09-16 出版日期:2017-11-26
  • 通信作者: 徐新娟
  • 基金资助:
    新疆维吾尔自治区科技支撑计划(201533104)

Relationship between cytochrome P450 3A5 gene polymorphism and the expected antihypertensive efficacy of amlodipine in hypertensive Kazak and Uygur patients in Xinjiang

Rongxiu Zhang1, Lanping Gu1, Xiaohuan Zhou1, Xinjuan Xu1,()   

  1. 1. Department of Hypertension, the first Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China
  • Received:2017-09-16 Published:2017-11-26
  • Corresponding author: Xinjuan Xu
  • About author:
    Corresponding author: Xu Xinjuan, Email:
引用本文:

张荣秀, 谷兰平, 周晓欢, 徐新娟. 新疆哈萨克族、维吾尔族高血压患者细胞色素P450 3A5基因多态性与氨氯地平预期降压疗效的关系[J]. 中华诊断学电子杂志, 2017, 05(04): 230-234.

Rongxiu Zhang, Lanping Gu, Xiaohuan Zhou, Xinjuan Xu. Relationship between cytochrome P450 3A5 gene polymorphism and the expected antihypertensive efficacy of amlodipine in hypertensive Kazak and Uygur patients in Xinjiang[J]. Chinese Journal of Diagnostics(Electronic Edition), 2017, 05(04): 230-234.

目的

探讨新疆哈萨克族、维吾尔族原发性高血压患者细胞色素P450 3A5(CYP3A5)基因多态性的民族差异与氨氯地平预期降压疗效的关系。

方法

选取2015年11月至2017年4月于新疆医科大学第一附属医院高血压科首次就诊的197例原发性高血压患者,其中哈萨克族99例、维吾尔族98例。提取患者外周血DNA,采用荧光定量聚合酶链式反应(PCR)技术及DNA测序技术检测CYP3A5基因多态性。采用卡方检验、Logistic回归的方法,分析样本中哈萨克族、维吾尔族原发性高血压患者CYP3A5基因型的民族差异及与氨氯地平预期降压疗效的关系。

结果

哈萨克族CYP3A5*3/*3基因型频率较维吾尔族频率高,分别为81.82%(81/99)、63.27%(62/98),差异有统计学意义(χ2=8.74,P=0.008)。调整基线血压、体质量指数、血脂、性别及年龄后,197例原发性高血压患者对氨氯地平预期疗效高度敏感、中度敏感、低度敏感的频率分别为77.16%(152/197),22.34%(44/197),0.51%(1/197);其中99例哈萨克族高血压患者为83.84%(83/99),16.16%(16/99),0.00%(0/99);98例维吾尔族高血压患者为70.41%(69/98),28.57%(28/98),1.02%(1/98);对氨氯地平预期疗效差异有统计学意义(χ2=5.46,P=0.033)。Logistic回归分析CYP3A5基因民族差异与氨氯地平预期降压疗效有相关性,具有统计学意义(OR=2.11,P=0.035)。

结论

新疆哈萨克族、维吾尔族原发性高血压患者CYP3A5基因存在民族差异,新疆哈萨克族原发性高血压患者较维吾尔族患者对氨氯地平敏感性更高。

Objective

To investigate the relationship between the ethnic difference in cytochrome P450 3A5(CYP3A5) gene polymorphism and the expected antihypertensive efficacy of amlodipine in patients with essential hypertension in Xinjiang Kazak and Uygur ethnic groups.

Methods

From November 2015 to April 2017, 197 palients with primary hypertension in the first Affiliated Hospital of Xinjiang Medical University were enrolled, of which Kazak 99 cases and Uygur 98 cases.Extracted peripheral blood DNA, PCR fluorescence probe technique and DNA sequencing were used to detect the polymorphism of CYP3A5 gene.The chi-square test and logistic regression were used to analyze the relationship between the ethnic difference in CYP3A5 gene polymorphism and the expected antihypertensive efficacy of amlodipine in patients with essential hypertension in Xinjiang Kazak and Uygur ethnic groups.

Results

The CYP3A5*3/*3 gene frequency of Kazak nationality(81.82%, 81/99) was significant higher than that in Uygur patients(63.27%, 62/98)(χ2=8.74, P=0.008). After adjusted for baseline blood pressure, body mass index, blood lipid, sex and age, the highly sensitive frequency, moderately sensitive frequency and low sensitive frequency of 197 cases of primary hypertension to the expected efficacy of amlodipine were 77.16%(152/197), 22.34%(44/197), 0.51%(1/197), respectively; 99 cases in Kazak patients with hypertension were 83.84%(83/99), 16.17%(16/99), 0.00%(0/99), respectively; 98 cases of Uygur patients with essential hypertension were 70.41%(69/98), 28.57%(28/98), 1.02%(1/98), respectively.The amlodipine was expected to have a statistically significant difference in therapeutic efficacy (χ2=5.46, P=0.033). Logistic regression showed that the CYP3A5 genetic national difference was associated with the expected antihypertensive efficacy of amlodipine (OR=2.11, P=0.035).

Conclusions

There is ethnic difference in CYP3A5 gene in Xinjiang Kazak and Uygur primary hypertension patients.The sensitivity of amlodipine in Xinjiang Kazak patients with hypertension is higher than that of Uygur patients.

表1 哈萨克族、维吾尔族患者一般资料比较(±s)
表2 哈萨克族、维吾尔族患者CYP3A5各基因型、基因频率和Hardy-Weinberg平衡检验
表3 CYP3A5基因型在哈萨克族、维吾尔族高血压组分布的比较(例,%)
表4 哈萨克族、维吾尔族原发性高血压患者对氨氯地平预期疗效比较(例,%)
表5 哈萨克族、维吾尔族原发性高血压患者对氨氯地平预期疗效的多因素Logisitc回归分析
[1]
Sukonthasarn A. A comparison of four primary classes of antihypertensive monotherapy in Thai patients[J]. J Med Assoe Thai, 2000, 83(10): 1202-1210.
[2]
Gonzalez FJ,Idle JR.Pharmacogenetic phenotyping and genotyping.Present status and future potential[J]. Clin Pharmacokinet, 1994, 26(1): 59-70.
[3]
Rioux PP.Clinial trials in pharmacogenetics and pharmacogenomies:methods and applications[J]. Am J Health Syst Pharm, 2000, 57(9): 887-898.
[4]
Lamba JK,Lin YS,Schuetz EG, et al.Genetic contribution to variable human CYP3A-mediated metabolism[J]. Adv Drug Deliv Rev, 2002, 54(10): 1271-1294.
[5]
Terrazzino S,Quaglia M,Stratta P, et al.The effect of CYP3A5 6986A>G and ABCB1 3435C>T on tacrolimus dose-adjusted trough levels and acute rejection rates in renal transplant patients: a systematic review and meta-analysis[J]. Pharmacogenet Genom, 2012, 22(8): 642-645.
[6]
Gellner K,Eiselt R,Hustert E, et al.Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene[J]. Pharmacogenetics, 2001, 11(2): 111-121.
[7]
Yamaori S,Yamazaki H,Suzuki A, et al.Effects of cytochrome b(5) on drug oxidation activities of human cytochrome P450 (CYP) 3As: similarity of CYP3A5 with CYP3A4 but not CYP3A7[J]. Biochem Pharmacol, 2003, 66(12): 2333-2340.
[8]
杨策,王海燕,杜娟, 等. 精准医学思维对创伤诊治模式的影响与前景[J/CD]. 中华诊断学电子杂志, 2015, 3(2): 98-101.
[9]
Koch I,Weil R,Wolbold R, et al.Interindividual variability and tissue-specificity in the expression of cytochrome P450 3A mRNA[J]. Drug Metab Dispos, 2002, 30(10): 1108-1114.
[10]
Tateishi T,Watanabe M,Moriya H, et al.No ethnic difference between Caucasian and Japanese hepatic samples in the expression frequency of CYP3A5 and CYP3A7 proteins[J]. Biochem Pharmacol, 1999, 57(8): 935-939.
[11]
Huang W,Lin YS,Calamia J C, et al.Evidence of significant contribution from CYP3A5 to hepatic drug metabolism[J]. Drug Metab Dispos, 2004, 32(12): 1434-1445.
[12]
Saeki M,Saito Y,Nakamura T, et al.Single nucleotide polymorphisms and haplotype frequencies of CYP3A5, in a Japanese population[J]. Hum Mut, 2003, 21(6): 653-660.
[13]
Kamide K,Yang J,Matayoshi T, et al.Genetic polymorphisms of L-type calcium channel alpha1C and alpha1D subunit genes are associated with sensitivity to the antihypertensive effects of L-type dihydropyridine calcium-channel blockers[J]. Circ J, 2009, 73(4): 732-740.
[14]
Burk O,Koch I,Raucy J, et al.The induction of cytochrome P450 3A5 (CYP3A5) in the human liver and intestine is mediated by the xenobiotic sensors pregnane X receptor (PXR) and constitutively activated receptor (CAR)[J]. J Biol Chem, 2004, 279(37): 38379-38385.
[15]
Simpson D,Noble S. Tacrolimus ointment: a review of its use in atopic dermatitis and its clinical potential in other inflammatory skin conditions[J]. Drugs, 2005, 65(6): 827-858.
[16]
Langaee TY,Gong Y,Yarandi HN, et al.Association of CYP3A5 Polymorphisms with Hypertension and Antihypertensive Response to Verapamil[J]. Clin Pharmacol2007, 81(3): 386-391.
[17]
Motshoge T,Tawe L,Muthoga CW, et al.Cytochrome P450 2C8*2 allele in Botswana: human genetic diversity and public health implications[J]. Acta Trop, 2016, 157: 54-58.
[18]
Kuehl P,Zhang J,Lin Y, et al.Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression[J]. Nat Genet, 2001, 27(4): 383-391.
[19]
储小曼,闵佩清,张静, 等. 药物代谢酶CYP3A在中国肾移植人群的遗传多态性[J]. 医学研究生学报, 2005, 18(2): 107-111.
[20]
Yamaori S,Yamazaki H,Suzuki A, et al.Effects of cytochrome b(5) on drug oxidation activities of human cytochrome P450 (CYP) 3As: similarity of CYP3A5 with CYP3A4 but not CYP3A7[J]. Biochem Pharmacol, 2003, 66(12): 2333-2340.
[21]
Fukushima-Uesaka H,Saito Y,Watanabe H, et al.Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese population[J]. Hum Mutat, 2004, 23(1): 100.
[22]
Xie HG,Wood AJ,Kim RB, et al.Genetic variability in CYP3A5 and its possible consequences[J]. Pharmacogenomics, 2004, 5(3): 243-272.
[23]
Hu YF,He J,Chen GL, et al.CYP3A5*3 and CYP3A4*18 single nucleotide polymorphisms in a Chinese population[J]. Clinica Chimica Acta, 2005, 353(1-2): 187-192.
[24]
Kim KA,Park PW,Lee OJ, etal.Effect of CYP3A5*3 genotype on the pharrnacokinetics and pharmacodynamics of in amlodipine in healthy Korean subjects[J]. Clin Pharmacol Ther, 2006, 80(6): 646-656.
[25]
Kim KA,Park PW,Lee OJ, et al.Effect of polymorphic CYP3A5 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects[J]. J Clin Pharmacol, 2007, 47(1): 87-93.
[26]
文娟,黄志军,袁洪, 等. 肾移植后高血压人群中CYP3A4*1G、CYP3A5*3和MDR1 C3435T基因多态性对氨氯地平降压疗效的影响[J]. 中国动脉硬化杂志, 2011, 19(1): 55-60.
[27]
Zhao Y,Zhai D,He H, et al.Effects of CYP3A5, MDR1 and CACNA1C polymorphisms on the oral disposition and response of nimodipine in a Chinese cohort[J]. Eur J Clin Pharmacol, 2009, 65(6): 579-584.
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