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伊朗健康人群中细胞色素P450酶2C9和2C19的基因多态性

Genetic polymorphisms of cytochrome P450 enzymes 2C9 and 2C19 in a healthy Iranian population.

作者信息

Zand Negin, Tajik Nader, Moghaddam Alireza Salek, Milanian Iraj

机构信息

Department of Pharmacology, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Clin Exp Pharmacol Physiol. 2007 Jan-Feb;34(1-2):102-5. doi: 10.1111/j.1440-1681.2007.04538.x.

Abstract
  1. The genetically polymorphic cytochrome P450 enzymes 2C9 (CYP2C9) and 2C19 (CYP2C19) are involved in the metabolism and elimination of a number of widely used drugs. The polymorphisms give rise to substantial interindividual and interethnic variability in drug excretion rates and final serum concentrations. For this reason, therapeutic responses and adverse drug reactions may vary from one person to another. In the present study we determined CYP2C9 and CYP2C19 genotypes in a random Iranian population to compare allele frequencies with previous findings in other ethnic groups. 2. Allelic variants of CYP2C9 (1/2/3) and CYP2C19 (1/2/3) were determined in 200 unrelated healthy Iranian volunteers by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. 3. Fifteen subjects (7.5%) were homozygous for the CYP2C92 allele, whereas 21 individuals (10.5%) were heterozygous for this allele and 164 subjects (82%) had the wild-type allele (CYP2C91). No CYP2C93 was detected in the population sampled. Six subjects (3%) were homozygous for CYP2C192, whereas 44 individuals (22%) were heterozygous for this allele. In the remaining subjects (75%), no CYP2C192 was found. In addition, no CYP2C193 was detected in the population sampled. 4. Based on our data, the frequency of the CYP2C92 allelic variant in Iranians is similar to that in other Caucasian populations; however, the frequency of the CYP2C93 allele differed significantly (P < 0.05). Conversely, there was no difference in the frequency of CYP2C19 allelic variants between the present study and other studies evaluating this allele in Caucasian populations (P > 0.05).
摘要
  1. 基因多态性细胞色素P450酶2C9(CYP2C9)和2C19(CYP2C19)参与多种广泛使用药物的代谢和消除。这些多态性导致药物排泄率和最终血清浓度在个体间和种族间存在显著差异。因此,治疗反应和药物不良反应可能因人而异。在本研究中,我们测定了伊朗随机人群中的CYP2C9和CYP2C19基因型,以比较等位基因频率与其他种族群体先前的研究结果。2. 通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析,在200名无亲缘关系的健康伊朗志愿者中测定了CYP2C9(1/2/3)和CYP2C19(1/2/3)的等位基因变体。3. 15名受试者(7.5%)为CYP2C92等位基因纯合子,21名个体(10.5%)为该等位基因杂合子,164名受试者(82%)具有野生型等位基因(CYP2C91)。在所采样的人群中未检测到CYP2C93。6名受试者(3%)为CYP2C192纯合子,44名个体(22%)为该等位基因杂合子。在其余受试者(75%)中,未发现CYP2C192。此外,在所采样的人群中未检测到CYP2C193。4. 根据我们的数据,伊朗人群中CYP2C92等位基因变体的频率与其他高加索人群相似;然而,CYP2C93等位基因的频率差异显著(P < 0.05)。相反,本研究与其他评估高加索人群中该等位基因的研究相比,CYP2C19等位基因变体的频率没有差异(P > 0.05)。

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