Association between cytochrome P450 (CYP) 2C19 polymorphisms and harm avoidance in Japanese.

Polymorphic enzyme cytochrome P450 (CYP) 2C19 is expressed not only in the liver but also in the brain and mediates the biotransformation of 5-hydroxytriptamine (5-HT). We investigated possible association between genetic polymorphism of CYP2C19 and individual personality traits, possibly influenced by neurotransmitters. Mentally and physically healthy Japanese subjects were enrolled in this study (n = 352). Temperament and Character Inventory (TCI) and CYP2C19 genotyping were performed in all subjects. We detected CYP2C19*2 and *3 (http://www.imm.ki.se/CYPalleles/) using Amplichip CYP450 DNA tip. The number of genotypes classified as homozygous extensive metabolizer (EM), heterozygous EM, and poor metabolizer were 113, 181, and 58, respectively. Significant difference was found in TCI score in harm avoidance (HA; F = 3.138, P < 0.05). Post hoc analysis showed that TCI score in harm avoidance in homozygous EM was significantly lower than that in heterozygous EM (P < 0.05) or PM (P < 0.05). In sub-item analyses, HA3 (shyness with strangers, P < 0.01) and HA1 (anticipatory worry, P < 0.05) of TCI scores were significantly different among CYP2C19 genotypes. Meanwhile, there were no differences in TCI scores of novelty seeking (NS; F = 0.350, n.s.), reward dependence (RD; F = 1.080, n.s.), or persistence (P; F = 0.786, n.s.) among CYP2C19 genotypes. This study demonstrated that a significant association between CYP2C19 activity and HA is present in Japanese. Copyright 2007 Wiley-Liss, Inc.