Association between the functional polymorphism (C3435T) of the gene encoding P-glycoprotein (ABCB1) and major depressive disorder in the Japanese population
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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DOI：
10.1016/j.jpsychires.2012.01.012
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发表时间：
2012-04-01
影响因子：
4.8
通讯作者：
Kunugi, Hiroshi
中科院分区：
文献类型：
--
作者：
Fujii, Takashi;Ota, Miho;Kunugi, Hiroshi
人P-糖蛋白（P-gp）由ABCB 1（ATP结合盒，亚家族B成员1）编码，表达于血脑屏障，作为外排泵保护脑免受包括糖皮质激素在内的多种药物和毒素的伤害。我们研究了ABCB 1的功能多态性是否会导致重度抑郁症（MDD）的易感性。5个功能性单核苷酸多态性（SNP）分别为A-41 G（rs 2188524）、T-129 C（rs3213619）、C1236 T（Gly 412 Gly：rs 1128503）。G2677 A/T（Ala 893 Ser/Thr：rs 2032582）和C3435 T（Ile 1145 Ile：rs 1045642）基因分型在631名日本MOD患者和1100名对照中进行。通过焦磷酸测序对三等位基因SNP G2677 A/T进行基因分型，并通过TaqMan 5 '-核酸外切酶等位基因鉴别测定对其余SNP进行基因分型。与对照组相比，MDD患者的次要T3435等位基因显著增加（chi（2）= 4.5，df = 1，p = 0.034，比值比[OR] 1.16，95%置信区间[CI] 1.01-1.34）。T3435等位基因的纯合子在患者中比对照组明显更常见（chi（2）= 7.5，df = 1，p = 0.0062，OR 1.43，95%CI 1.11-1.85）。其他4个SNP的基因型和等位基因分布差异均无统计学意义。在基于单倍型的分析中，患者中具有TT 1236-TT 3435单倍型基因型的个体比例显著高于对照组（chi（2）= 8.5，df = 1，p = 0.0037，OR 1.50，95%CI 1.14-1.98）。我们的研究结果表明，T3435等位基因或携带该等位基因的两个拷贝赋予易感性MOD在日本人口。(C)2012爱思唯尔有限公司保留所有权利。
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 MOD 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 (chi(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 (chi(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 (chi(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 MOD in the Japanese population. (C) 2012 Elsevier Ltd. All rights reserved.