title: Implication of P-glycoprotein in formation of depression-prone personality: association study between the C3435T MDR1 gene polymorphism and interpersonal sensitivity.
abstract: OBJECTIVE
  Interpersonal sensitivity is defined as undue and excessive awareness of, and sensitivity to, the behavior and feelings of others. Previous studies suggested that interpersonal sensitivity is one of the vulnerable factors to depression, and that genetic factors and cortisol are involved in the formation of interpersonal sensitivity. On the other hand, P-glycoprotein, which is encoded by the multidrug resistance 1 (MDR1) gene, serves as a barrier to entry and as an active eliminator for xenobiotics and cellular metabolites including cortisol, which is implicated in multiple brain functions. In the present study, we examined the effects of the MDR1 C3435T polymorphism (rs1045642) on interpersonal sensitivity in healthy subjects.
  
  
  METHODS
  The subjects were 842 healthy Japanese volunteers (mean age = 26.7 years, male/female ratio = 490/352). The C3435T polymorphism of MDR1 gene was detected by a PCR method, and interpersonal sensitivity was assessed by the Interpersonal Sensitivity Measure (IPSM).
  
  
  RESULTS
  The 2-factor analysis of covariance (ANCOVA) showed a significant main effect of the MDR1 genotype on the IPSM scores with a significant interaction between the genotype and gender. The subsequent 1-factor ANCOVA showed that in females the C/C genotype group had higher IPSM scores than the C/T genotype group (p < 0.001) and the T/T genotype group (p < 0.001), and the C/T genotype group had higher IPSM scores than the T/T genotype group (p = 0.014). In males no significant association was found between the MDR1 genotype and the IPSM scores. In allelic analyses using the χ(2) tests, the C allele frequency in females was significantly higher (p < 0.001) in the high IPSM group than in the low IPSM group, while there was no significant difference in the C allele frequency between the high and low IPSM groups in total subjects and males.
  
  
  CONCLUSIONS
  The present study suggests that the C3435T polymorphism of the MDR1 gene affects the formation of a depression-prone personality trait in Japanese females.
authors.affiliation: Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Enokido
authors.forename: Akihito
authors.initials: A
authors.lastname: Suzuki
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Sadahiro
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Naoshi
authors.initials: N
authors.lastname: Shibuya
authors.forename: Kaoru
authors.initials: K
authors.lastname: Goto
authors.forename: Koichi
authors.initials: K
authors.lastname: Otani
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D003863:Depression / Q000235:genetics* / Q000523:psychology*; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D007398:Interpersonal Relations; D007564:Japan; D008297:Male; D010551:Personality / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011581:Psychological Tests; D012737:Sex Factors
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B