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1. J Psychiatr Res. 2012 Feb 3. [Epub ahead of print]

Association between the functional polymorphism (C3435T) of the gene encoding
P-glycoprotein (ABCB1) and major depressive disorder in the Japanese population.

Fujii T, Ota M, Hori H, Sasayama D, Hattori K, Teraishi T, Yamamoto N, Hashikura
M, Tatsumi M, Higuchi T, Kunugi H.

Department of Mental Disorder Research, National Institute of Neuroscience,
National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo
187 8502, Japan.

Human P-glycoprotein (P-gp), which is encoded by ABCB1 (ATP-binding cassette,
sub-family B member 1), is expressed in the blood brain barrier and protects the
brain from many kinds of drugs and toxins including glucocorticoids by acting as
an efflux pump. We examined whether functional polymorphisms of ABCB1 give
susceptibility to major depressive disorder (MDD). The five functional single
nucleotide polymorphisms (SNPs), A-41G (rs2188524), T-129C (rs3213619), C1236T
(Gly412Gly: rs1128503), G2677A/T (Ala893Ser/Thr: rs2032582), and C3435T
(Ile1145Ile: rs1045642) were genotyped in 631 MDD patients and 1100 controls in
the Japanese population. A tri-allelic SNP, G2677A/T, was genotyped by
pyrosequencing and the remaining SNPs were genotyped by the TaqMan 5'-exonuclease
allelic discrimination assay. The minor T3435 allele was significantly increased
in MDD patients than in the controls (χ(2) = 4.5, df = 1, p = 0.034, odds ratio
[OR] 1.16, 95% confidential interval [CI] 1.01-1.34). Homozygotes for the T3435
allele was significantly more common in patients than in the controls
(χ(2) = 7.5, df = 1, p = 0.0062, OR 1.43, 95%CI 1.11-1.85). With respect to the
other 4 SNPs, there was no significant difference in genotype or allele
distribution. In the haplotype-based analysis, the proportion of individuals with
the TT1236-TT3435 haploid genotype was significantly increased in patients than
in controls (χ(2) = 8.5, df = 1, p = 0.0037, OR 1.50, 95%CI 1.14-1.98). Our
results suggest that the T3435 allele or carrying two copies of this allele
confers susceptibility to MDD in the Japanese population.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID: 22306099 [PubMed - as supplied by publisher]