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约旦人群中某些单核苷酸多态性的频率及CYP2D6基因重复情况。

Frequency of certain single-nucleotide polymorphisms and duplication of CYP2D6 in the Jordanian population.

作者信息

Zihlif Malek, Imraish Amer, Irshaid Yacoub M

机构信息

Department of Pharmacology, University of Jordan, Amman, Jordan.

出版信息

Genet Test Mol Biomarkers. 2012 Oct;16(10):1201-5. doi: 10.1089/gtmb.2012.0122. Epub 2012 Aug 20.

DOI:10.1089/gtmb.2012.0122
PMID:22905959
Abstract

The CYP2D6 isozymes are responsible for metabolism of 7-10% of clinically available drugs. Genetic polymorphism in CYP2D6 may have an impact on drug efficacy and toxicity. The aim of this study was to determine the allelic frequency of CYP2D64, 10, and 17 and CYP2D62×N duplication allele in 192 healthy unrelated male and female Jordanian volunteers. Polymerase chain reaction (PCR)-restriction fragment length polymorphism-based methods were used to identify the CYP2D64, 10, and 17 genotypes; and allele-specific long PCR was used to determine the CYP2D62×N allelic frequency. The CYP2D610 allele was the most frequent mutant allele in Jordanians (14.8%) followed by CYP2D64 and 17 at 12.8%, and 8.3%, respectively. The duplication allele was found in 13.5% of the studied sample. The CYP2D64 G-A heterozygote genotype frequency was 20.3%, and the homozygous mutant genotype was 2.6%. In case of CYP2D610 C-T and CYP2D617 G-C heterozygote genotypes, the frequencies were 21.4% and 12.5%, respectively, while the homozygous mutant genotype frequencies of T-T and C-C were 4.2% and 2.1%, respectively. In conclusion, the allelic distributions of the CYP2D6 gene among Jordanians are different from other Mediterranean groups, especially the *10 and 17 single-nucleotide polymorphisms, and more importantly the CYP2D62×N duplication allele, which seems to follow a gradient reduction in prevalence from Ethiopia to Northern Europe.

摘要

细胞色素P450 2D6(CYP2D6)同工酶负责7%至10%的临床可用药物的代谢。CYP2D6基因多态性可能会影响药物疗效和毒性。本研究的目的是确定192名健康、无亲缘关系的约旦志愿者(男女均有)中CYP2D64、10和17以及CYP2D62×N重复等位基因的等位基因频率。采用基于聚合酶链反应(PCR)-限制性片段长度多态性的方法来鉴定CYP2D64、10和17基因型;采用等位基因特异性长PCR来确定CYP2D62×N等位基因频率。CYP2D610等位基因是约旦人中最常见的突变等位基因(14.8%),其次是CYP2D64和17,分别为12.8%和8.3%。在所研究样本的13.5%中发现了重复等位基因。CYP2D64 G-A杂合子基因型频率为20.3%,纯合突变基因型频率为2.6%。对于CYP2D610 C-T和CYP2D617 G-C杂合子基因型,频率分别为21.4%和12.5%,而T-T和C-C的纯合突变基因型频率分别为4.2%和2.1%。总之,CYP2D6基因在约旦人中的等位基因分布与其他地中海群体不同,尤其是10和17单核苷酸多态性,更重要的是CYP2D6*2×N重复等位基因,其流行率似乎从埃塞俄比亚到北欧呈梯度下降。

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