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

• Published in: European Journal of Clinical Pharmacology
• Language: English
• Published: Springer-Verlag 2011
• Subjects: CYP2C haplotypes; CYP2C19*17; Linkage disequilibrium; Allele frequencies; Faroe Islands; Norway; Petersen; Pedersen; Kristensen; Torshavn
• Online Access: http://hdl.handle.net/2262/58011; https://doi.org/10.1007/s00228-010-0864-8

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 CYP2C8*3, CYP2C9*2, CYP2C9*3, and CYP2C19*2 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 CYP2C8*1, CYP2C9*1, and CYP2C19*1. The second most frequent haplotype (19%) is composed of CYP2C19*17, CYP2C8*1, and CYP2C9*1. This predicted haplotype accounts for 99.7% of the CYP2C19*17 alleles found in the 896 subjects. Conclusion CYP2C19*17 is a frequent genetic variant in Nordic populations that exists in strong linkage disequilibrium with wildtype CYP2C8*1 and CYP2C9*1 alleles, which effectively makes it a determinant for a haplotype exhibiting an efficient CYP2C substrate metabolism. phone: [phone] (Pedersen, Rasmus S.) [e-mail] (Pedersen, Rasmus S.) Institute of Public Health, Clinical Pharmacology, University of Southern Denmark - Odense - DENMARK (Pedersen, Rasmus S.) Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet - Stockholm - SWEDEN (Pedersen, Rasmus S.) Institute of Public Health, Clinical Pharmacology, University of Southern Denmark - Odense - DENMARK (Brasch-Andersen, Charlotte) Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet - Stockholm - SWEDEN (Sim, Sarah C.) Institute of Public Health, Clinical Pharmacology, University of Southern Denmark - Odense - DENMARK (Bergmann, Troels K.) Institute of Public Health, Clinical Pharmacology, University of Southern Denmark - Odense - DENMARK (Halling, Jonrit) Department of Occupational Medicines and Public Health, The Faroese Hospital System - Torshavn - FAROE ISLANDS (Halling, Jonrit) Institute of Public Health, Clinical Pharmacology, University of Southern Denmark - Odense - DENMARK (Petersen, Maria S.) Department of Occupational Medicines and Public Health, The Faroese Hospital System - Torshavn - FAROE ISLANDS (Petersen, Maria S.) Department of Occupational Medicines and Public Health, The Faroese Hospital System - Torshavn - FAROE ISLANDS (Weihe, Pal) Department of Genetics, Institute of Cancer Research, Oslo University Hospital Radiumhospitalet - Oslo - NORWAY (Edvardsen, Hege) Institute of Clinical Medicine, University of Oslo - Oslo - NORWAY (Edvardsen, Hege) Department of Genetics, Institute of Cancer Research, Oslo University Hospital Radiumhospitalet - Oslo - NORWAY (Kristensen, Vessela N.) Institute of Clinical Medicine, University of Oslo - Oslo - NORWAY (Kristensen, Vessela N.) EpiGen, Institute for Clinical Medicine, Akershus University Hospital - Oslo - NORWAY (Kristensen, Vessela N.) Institute of Public Health, Clinical Pharmacology, University of Southern Denmark - Odense - DENMARK (Br?sen, Kim) Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet - Stockholm - SWEDEN (Ingelman-Sundberg, Magnus) DENMARK FAROE ISLANDS NORWAY SWEDEN Registration: 2010-07-02 Received: 2010-06-03 Accepted: 2010-07-01 ePublished: 2010-07-28