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

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• 作者：Takashi Fujii^a ; Miho Ota^a ; Hiroaki Hori^a ; ^b ; Daimei Sasayama^a ; Kotaro Hattori^a ; Toshiya Teraishi^a ; Noriko Yamamoto^a ; Miyako Hashikura^a ; Masahiko Tatsumi^c ; Teruhiko Higuchi^d ; Hiroshi Kunugi^a ; ^b ; ^{hkunugi@ncnp.go.jp}
• 关键词：P-glycoprotein ; ABCB1 ; Major depressive disorder ; Functional polymorphism ; Genetic association
• 刊名：Journal of Psychiatric Research
• 出版年：2012
• 期刊代码：169_00223956
• 类别：med
• 出版时间：April, 2012
• 卷：46
• 期：4
• 页码：555-559
• 文件大小：278 K

摘要

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鈥?exonuclease allelic discrimination assay. The minor T3435 allele was significantly increased in MDD patients than in the controls (蠂²聽=聽4.5, df聽=聽1, p聽=聽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 (蠂²聽=聽7.5, df聽=聽1, p聽=聽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 (蠂²聽=聽8.5, df聽=聽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.