J Psychiatr Res. 2012 Apr;46(4):555-9. doi: 10.1016/j.jpsychires.2012.01.012. Epub 2012 Feb 4.
Association between the functional polymorphism (C3435T) of the gene encoding P-glycoprotein (ABCB1) and major depressive disorder in the Japanese population.
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.
私たちは今回、血液脳関門のストレスホルモン排出ポンプであるP 糖タンパク質(ABCB1)の機能低下型遺伝子について、日本人の「大うつ病性障害」患者631 人、健常者1100 人を対象として解析し、機能低下型対立遺伝子(アリル)T3435(rs045642)は患者群に有意に多くみられること、さらに父親と 母親双方からこのアリルを受け継いでいる人の頻度も、患者に有意に多くみられることを示した。この結果が他のサンプルでも再現されれば、うつ病発症の分子メカニズム解明と、その後の治療への応用を切り開く上で、重要な意味を持つ。