近日，国际著名杂志Journal of Psychiatric Research在线刊登了日本国立精神神经医疗研究中心研究人员的最新研究成果“Association between the functional polymorphism (C3435T) of the gene encoding P-glycoprotein (ABCB1) and major depressive disorder in the Japanese population，”，文章中，研究者功刀浩研究员通过可排解大脑应激物质的P糖蛋白研究，分析日本抑郁患者的遗传基因，发现里面存在一种被称为“ABCB1”的基因，该基因致使P糖蛋白功能下降的DNA发生变异，导致抑郁症发生。掀开该原理，有望找到治疗抑郁症的新方法。
专家对日本631名抑郁症患者和1100名正常人的遗传基因进行解析，许多患者的基因显示，在带有ABCB1的DNA某个特定场所发生了胞嘧啶向胸腺嘧啶的置换。生物体出现应激，血液中释放出一种被称为糖皮质激素的应激物质，本来P糖蛋白具有将侵入大脑的糖皮质激素排出大脑的功能，可一旦带有变异性的ABCB1后，大脑里的糖皮质激素上升，诱发抑郁症的可能性增大。
功刀浩研究员称，亚洲和欧洲人中，也许一半的人带有同类基因的变异，也就是说许多人存在患抑郁症的风险基因。（生物谷Bioon.com）
doi:10.1016/j.jpsychires.2012.01.012
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Association between the functional polymorphism (C3435T) of the gene encoding P-glycoprotein (ABCB1) and major depressive disorder in the Japanese population
Takashi Fujiia, Miho Otaa, Hiroaki Horia, b, Daimei Sasayamaa, Kotaro Hattoria, Toshiya Teraishia, Noriko Yamamotoa, Miyako Hashikuraa, Masahiko Tatsumic, Teruhiko Higuchid, Hiroshi Kunugia, b, ,
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 (χ2 = 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 (χ2 = 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 (χ2 = 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.
