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The prevalence of CYP2C19 genotypes in a population of healthy Dutch volunteers and apparent gender differences in phenotypes
Author(s) -
Tamminga Wim J.,
Wemer Johan,
Oosterhuis Berend,
De Zeeuw Rokus A.,
De Leij Lou F. M. H.,
Jonkman Jan H. G.
Publication year - 2002
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2002.161312.x
Subject(s) - cyp2c19 , genotyping , genotype , allele , population , medicine , polymorphism (computer science) , genetics , allele frequency , biology , gene , environmental health
We reported the prevalence of poor metabolizers of CYP2C19 to be 1.8% in a sample of the Dutch population ( n =4301; [1]). These data were obtained by phenotyping. In that study pronounced oral contraceptive related gender differences for CYP2C19 activity were reported. The present study was performed to estimate the prevalence of non‐coding mutations of CYP2C19 leading to the poor metabolizer phenotype. Furthermore, the data were analysed for gender differences. Seven hundred and sixty‐five unrelated healthy volunteers were evaluated for their CYP2C19 status. Subjects were phenotyped using mephenytoin. Genotyping was performed by the polymerase chain reaction (PCR) and restriction analysis for the most common null alleles. For CYP2C19*2 and CYP2C19*3 a frequency of 13.3% and 0.2%, respectively, was observed. The S/R‐ratio was significantly higher in heterozygous subjects (S/R‐ratio=0.22) compared with homozygous wild type subjects (S/R‐ratio=0.11). Comparison of all subjects below 45 years showed a significantly higher S/R‐ratio in females compared with males especially in heterozygous subjects (S/R‐ratio: 0.39 vs 0.19; P <0.001). The frequencies of CYP2C19 allelic variants in a population of Dutch healthy volunteers were in accordance with data on other European populations. Assessment of * 2 and * 3 for CYP2C19 predicted the phenotype with an accuracy of over 98.6%. Gene‐dose effect existed for CYP2C19. CYP2C19 heterozygous females had a decreased CYP2C19 activity that may be at least partly due to the use of oral contraceptives.