1022-7954/05/4107- © 2005 Pleiades Publishing, Inc. 0789 Russian Journal of Genetics, Vol. 41, No. 7, 2005, pp. 789–793. Translated from Genetika, Vol. 41, No. 7, 2005, pp. 966–972. Original Russian Text Copyright © 2005 by Golimbet, Gritsenko, Alfimova, Ebstein. INTRODUCTION At present, conclusive evidence has been obtained testifying to a significant contribution of hereditary fac- tors to human psychological features, including person- ality traits. According to the results of psychological genetic research, heritabilities of personality traits range from 30 to 60%. As other psychological charac- teristics, personality traits show quantitative inherit- ance that depends on the combined effect or interaction of numerous minor genes. Extensive studying of molecular–genetic prerequisites of personality was associated with the discovery of genes encoding pro- teins with known functions in the biochemical pro- cesses of the brain. The psychobiological model by S.R. Cloninger has related these genes to particular per- sonality traits. Distinguishing four of these traits: harm avoidance, novelty seeking, reward dependence, and persistence, this author suggested that harm avoidance is associated with the serotonin brain system; novelty seeking, with the dopamine system; and reward depen- dence, with the noradrenaline system. To assess these traits, Cloninger developed Tridimentional Personality Questionnaire (TPQ), and later, Temperament and Character Inventory (TCI). Individuals scoring high on the Harm Avoidance scale are characterized by high anticipational anxiety, shyness, easy tiredness, fear of danger and the unknown (the positive extreme being optimism, courage, and drive). Individuals with high novelty seeking scores exhibit curiosity, spontaneity, irritability; they tend to break rules banning their access to what they perceive as pleasurable or exciting (the opposite extreme: conventionality, acceptance of rules). Individuals scoring high on the reward dependence scale are ready to form close interpersonal relation- ships, sensitive and sentimental (the opposite extreme: aloofness, independence, criticism). Persons scoring high and low on the persistence scale tend to easily abandon their goal after encountering hurdles. Note that the novelty seeking trait is somewhat sim- ilar to characteristics included in other generally known psychological models of personality. In particular, this trait shows high correlation with extraversion in G. Eysenck’s model (Eysenck Personality Inventory, EPI) [1, 2]. The first confirmation of Cloninger’s model was found for the D4 dopamine receptor gene (DRD4). Ebstein et al. [2] have recorded association of the poly- morphic region represented by a 48-bp VNTR marker in Polymorphic Markers of the Dopamine D4 Receptor Gene Promoter Region and Personality Traits in Mentally Healthy Individuals from the Russian Population V. E. Golimbet 1 , I. K. Gritsenko 2 , M. V. Alfimova 1 , and R. P. Ebstein 2 1 Research Mental Health Center, Russian Academy of Medical Sciences, Moscow, 113152 Russia; fax: (095) 952-89-40; e-mail: golimbet@online.ru 2 Scheinfeld Center of Human Genetics in the Social Sciences, Department of Psychology, Hebrew University, Jerusalem, 91905 Israel Received June 23, 2004 Abstract—The dopamine receptor gene D4 is a highly polymorphic gene, which, according to a number of studies, is associated with the personality traits characterizing human activity. Earlier, a VNTR polymorphic marker in exon 3 and single-nucleotide polymorphism in the promoter region were shown to be associated with novelty seeking. However, these results were not supported by all subsequent studies, which suggest a possible effect of other polymorphic regions of this gene. The aim of the present work was studying the effect of gene DRD4 on activity-related human personality traits in Russians, using in association analysis three polymorphic markers of this gene (–809 G/A, –616 C/G, and –521 C/T) and psychological traits assessed by various tests. Genotyping and psychological examination were conducted in 220 mentally healthy subjects (131 individuals lacking hereditary load of psychic diseases and 89 relatives of patients with psychoses). In Russians, allele fre- quencies of all markers proved to have no significant difference from the corresponding estimates for European populations. The markers examined were in linkage equilibrium. We have found a significant contribution of genotypes –521 C/T and –809 G/A to the expression of extraversion (Eysenck Personality Inventory (EPI), P = 0.0016) and variation of scores of the Social Introversion scale (Minnesota Multiphase Personality Inventory (MMPI), P = 0.0085). Genotypes –521 C/T and –616 C/G had a joint effect on scores on the Hypomania scale (P = 0.04), while their effect on extraversion was recorded as a trend (P = 0.054). Thus, the results of this study in general support the evidence by other authors showing association of polymorphism at the DRD4 gene promoter to personality traits. We have shown that the traits in question were mainly related to social activity. A reduction in social activity is associated largely with the í(–521 C/T) allele, characterized by low transcription rate. HUMAN GENETICS