CYP2C19*17 等位基因与野生型 CYP2C8 和 CYP2C9 等位基因之间的连锁不平衡：在健康北欧人群中鉴定 CYP2C 单倍型。

Linkage disequilibrium between the CYP2C19*17 allele and wildtype CYP2C8 and CYP2C9 alleles: identification of CYP2C haplotypes in healthy Nordic populations.

机构信息

Institute of Public Health, Clinical Pharmacology, University of Southern Denmark, Odense, Denmark.

出版信息

Eur J Clin Pharmacol. 2010 Dec;66(12):1199-205. doi: 10.1007/s00228-010-0864-8. Epub 2010 Jul 28.

DOI:10.1007/s00228-010-0864-8

PMID:20665013

Abstract

PURPOSE

To determine the distribution of clinically important CYP2C genotypes and allele frequencies in healthy Nordic populations with special focus on linkage disequilibrium.

METHODS

A total of 896 healthy subjects from three Nordic populations (Danish, Faroese, and Norwegian) were genotyped for five frequent and clinically important CYP2C allelic variants: the defective CYP2C83, CYP2C92, CYP2C93, and CYP2C192 alleles, and the CYP2C19*17 allele that causes rapid drug metabolism. Linkage disequilibrium was evaluated and CYP2C haplotypes were inferred in the entire population.

RESULTS

Ten CYP2C haplotypes were inferred, the most frequent of which (49%) was the CYP2C wildtype haplotype carrying CYP2C81, CYP2C91, and CYP2C191. The second most frequent haplotype (19%) is composed of CYP2C1917, CYP2C81, and CYP2C91. This predicted haplotype accounts for 99.7% of the CYP2C19*17 alleles found in the 896 subjects.

CONCLUSION

CYP2C1917 is a frequent genetic variant in Nordic populations that exists in strong linkage disequilibrium with wildtype CYP2C81 and CYP2C9*1 alleles, which effectively makes it a determinant for a haplotype exhibiting an efficient CYP2C substrate metabolism.

摘要

目的

确定具有特殊关注连锁不平衡的健康北欧人群中临床重要 CYP2C 基因型和等位基因频率的分布。

方法

对来自三个北欧人群（丹麦、法罗群岛和挪威）的 896 名健康受试者进行了五种常见且具有临床重要性的 CYP2C 等位基因变异的基因分型：缺陷 CYP2C83、CYP2C92、CYP2C93 和 CYP2C192 等位基因，以及导致快速药物代谢的 CYP2C19*17 等位基因。评估了连锁不平衡并推断了整个群体中的 CYP2C 单倍型。

结果

推断出了 10 种 CYP2C 单倍型，其中最常见的（49%）是携带 CYP2C81、CYP2C91 和 CYP2C191 的 CYP2C 野生型单倍型。第二常见的单倍型（19%）由 CYP2C1917、CYP2C81 和 CYP2C91 组成。该预测单倍型占 896 名受试者中发现的 CYP2C19*17 等位基因的 99.7%。