近日,，國際著名雜志Journal of Psychiatric Research在線刊登了日本國立精神神經(jīng)醫(yī)療研究中心研究人員的最新研究成果“Association between the functional polymorphism (C3435T) of the gene encoding P-glycoprotein (ABCB1) and major depressive disorder in the Japanese population，”,，文章中,，研究者功刀浩研究員通過可排解大腦應激物質的P糖蛋白研究，分析日本抑郁患者的遺傳基因,，發(fā)現(xiàn)里面存在一種被稱為“ABCB1”的基因,，該基因致使P糖蛋白功能下降的DNA發(fā)生變異，導致抑郁癥發(fā)生,。掀開該原理,，有望找到治療抑郁癥的新方法。
專家對日本631名抑郁癥患者和1100名正常人的遺傳基因進行解析,，許多患者的基因顯示,，在帶有ABCB1的DNA某個特定場所發(fā)生了胞嘧啶向胸腺嘧啶的置換。生物體出現(xiàn)應激,，血液中釋放出一種被稱為糖皮質激素的應激物質,，本來P糖蛋白具有將侵入大腦的糖皮質激素排出大腦的功能，可一旦帶有變異性的ABCB1后,，大腦里的糖皮質激素上升,，誘發(fā)抑郁癥的可能性增大。
功刀浩研究員稱,，亞洲和歐洲人中,，也許一半的人帶有同類基因的變異，也就是說許多人存在患抑郁癥的風險基因,。（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.
