Investigation of allele and genotype frequencies of CYP2C9, CYP2C19 and VKORC1 in Iran
Investigation of allele and genotype frequencies of CYP2C9, CYP2C19 and VKORC1 in Iran
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DOI：
10.1016/s1734-1140(10)70332-7
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发表时间：
2010-07-01
影响因子：
4.4
通讯作者：
Darai, Masumeh
中科院分区：
文献类型：
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作者：
Azarpira, Negar;Namazi, Soha;Darai, Masumeh
研究表明，在编码代谢酶的基因中，高功能突变的频率存在显著的种族差异。然而，很少有研究探讨了伊朗人口内的主要等位基因变异的频率分布。本研究集中在伊朗南部的基因型谱，以比较CYP 2C 9，CYP 2C 19和VKORC 1 - 1639 G>A（所有这些都已被证明在华法林代谢中具有重要作用）与其他人群的等位基因频率。因此，采用聚合酶链反应-限制性长度多态性（PCR-RFLP）对150例受试者（50例健康志愿者和100例门诊受试者）进行基因分型。结果表明，在南部和北方伊朗人之间的CYP 2C 9，CYP 2C 19和VKORC 1的多态性等位基因的分布的相似性和差异。例如，发现伊朗南部人中CYP 2C 9 *3的频率（9.8%）与高加索人（在这种情况下，意大利人）中发现的频率（9.7%）相似，但高于非洲人（1%），日本人（2.3%）和北方伊朗人（0%）中发现的频率。这些发现证实了伊朗南部和北方人之间CYP 2C 9频率的显著种族间差异。我们受试者中报告的CYP 2C 9 *2频率（25.3%）与高加索人（10-13%）、非洲人（2%）和亚洲人（0%）人群中观察到的频率不同。CYP 2C 19 *2和CYP 2C 19 *3等位基因频率与高加索人群相似。VKORC 1 - 1639 A等位基因频率（55.6%）与白种人一致，但与中国人（96%）和非洲裔美国人（13%）不同，这一发现证实了药物清除代谢能力的一些重要种族差异。由于伊朗人口由几个种族组成，这种类型的分析可以帮助解释北方和伊朗南部人口之间的遗传多样性。此外，本研究的结果将有助于了解伊朗人的临床药代动力学和药物剂量建议。
Research has shown that there are significant ethnic variations in the frequency of highly functional mutations in genes coding for metabolic enzymes. However, few studies have examined the frequency distribution of major allelic variations within the population of Iran. The present study focused on the genotype profile of southern Iranians in order to compare the allelic frequencies of CYP2C9, CYP2C19, and VKORC1 - 1639G>A (all of which have been shown to have significant roles in the metabolism of warfarin) with those of other populations. Therefore, genotyping was carried out on 150 subjects (50 healthy volunteers and 100 outpatient subjects) by polymerase chain reaction- restriction length polymorphism (PCR-RFLP). Findings indicated both similarities and differences in the distribution of polymorphic alleles of CYP2C9, CYP2C19 and VKORC1 between southern and northern Iranians. For example, the frequency of CYP2C9*3 among southern Iranians (9.8%) was found to be similar to the frequency found among Caucasians (in this case, Italians) (9.7%) but was higher than the frequency found among Africans (1%), Japanese (2.3%), and northern Iranians (0%). These findings confirmed significant inter-ethnic differences in CYP2C9 frequencies between southern and northern Iranians The reported frequency of CYP2C9*2 in our subjects (25.3%) was different from the frequencies seen in Caucasian (10-13%), African (2%) and Asian (0%) populations. The CYP2C19*2 and CYP2C19*3 allelic frequencies were similar to the Caucasian population. For VKORC1, the allelic frequency of-1639A (55.6%) was in accordance with Caucasian, but different from Chinese (96%) and African-American populations (13%).The findings confirmed some important interethnic differences in the metabolic capacity for drug clearance. Because the population of Iran consists of several ethnicities, this type of analysis can help explain the genetic diversity between the populations of northern and southern Iran. In addition, the results of this study will be useful for understanding clinical pharmacokinetics and drug dosage recommendations for Iranians.