Allele and genotype frequencies of CYP2B6 and CYP2C19 polymorphisms in Egyptian agricultural workers.

Allele and genotype frequencies of CYP2B6 and CYP2C19 polymorphisms in Egyptian agricultural workers.
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DOI:
10.1080/15287394.2012.641201
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发表时间:
2012
期刊:
Journal of toxicology and environmental health. Part A
影响因子:
--
通讯作者:
Olson JR
Olson JR
中科院分区:
其他
文献类型:
--
作者:
Ellison CA;Abou El-Ella SS;Tawfik M;Lein PJ;Olson JR

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细胞色素P-450(CYP 450)的遗传变异有可能改变对许多化学品的药理学和毒理学反应。CYP 2B 6和CYP 2C 19都具有代谢多种药物和环境污染物(包括有机磷(OP)农药毒死蜱)的能力,因此具有生物学和毒理学相关性。本研究的目的是确定CYP 2B 6和CYP 2C 19变异体在土著埃及人口(n = 120),被证明是职业暴露于毒死蜱的患病率。此外,将埃及人的基因型数据与之前研究的人群进行比较,以确定人群之间的差异。等位基因频率为CYP 2B 6 1459 C> T(3.8%)、CYP 2B 6 785 A> G(30.4%)、CYP 2B 6 516 G> T(28.8%)、CYP 2C 19 681 G> A(3.8%)和CYP 2C 19 431 G> A(0%)。最常见的CYP 2B 6基因型组合为CYP 2B 6 *1/*1(44%)、*1/*6(38%)、*6/*6(8%)和 *1/*5(6%)。CYP 2C 19基因型组合的频率为CYP 2C 19 *1/*1(93%)、*1/*2(6%)和 *2/*2(1%)。该埃及队列中CYP 2B 6 516 G> T和CYP 2B 6 785 A> G多态性的频率与北美和欧洲人群相似,但与西非人群报告的频率显著不同,而CYP 2B 6 1459 C> T与非洲人和非裔美国人相似。在埃及人中观察到的CYP 2C 19 681 G> A的频率与非洲俾格米人相似,但与其他世界人群显著不同,而CYP 2C 19 431 G > A与非洲俾格米人显著不同,但与其他世界人群相似。
Genetic variability in cytochrome P-450 (CYP) has the potential to modify pharmacological and toxicological responses to many chemicals. Both CYP2B6 and CYP2C19 are pharmacologically and toxicologically relevant due to their ability to metabolize multiple drugs and environmental contaminants, including the organophosphorus (OP) pesticide chlorpyrifos. The aim of this study was to determine the prevalence of CYP2B6 and CYP2C19 variants in an indigenous Egyptian population (n = 120) that was shown to be occupationally exposed to chlorpyrifos. Further, the genotyping data was compared for Egyptians with previously studied populations to determine between population differences. Allelic frequencies were CYP2B6 1459C > T (3.8%), CYP2B6 785A > G (30.4%), CYP2B6 516G > T (28.8%), CYP2C19 681G > A (3.8%), and CYP2C19 431G > A (0%). The most prevalent CYP2B6 genotype combinations were CYP2B6 *1/*1 (44%), *1/*6 (38%), *6/*6 (8%), and *1/*5 (6%). The frequency of the CYP2C19 genotype combinations were CYP2C19 *1/*1 (93%), *1/*2 (6%), and *2/*2 (1%). The frequency of the CYP2B6 516G > T and CYP2B6 785A > G polymorphisms in this Egyptian cohort is similar to that found North American and European populations but significantly different from that reported for West African populations, while that of CYP2B6 1459C > T is similar to that found in Africans and African Americans. The observed frequency of CYP2C19 681G > A in Egyptians is similar to that of African pygmies but significantly different from other world populations, while CYP2C19 431 G > A was significantly different from that of African pygmies but similar to other world populations.