Glycogen Synthase Kinase 3 Beta Gene Structural Variants as Possible Risk Factors of Bipolar Depression

被引:24
|
作者
Ronai, Zsolt [1 ]
Kovacs-Nagy, Reka [1 ]
Szantai, Eszter [1 ]
Elek, Zsuzsanna [1 ]
Sasvari-Szekely, Maria [1 ]
Faludi, Gabor [2 ]
Benkovits, Judit [3 ]
Rethelyi, Janos M. [3 ]
Szekely, Anna [4 ]
机构
[1] Semmelweis Univ, Inst Med Chem Mol Biol & Pathobiochem, H-1085 Budapest, Hungary
[2] Semmelweis Univ, Dept Clin & Theoret Mental Hlth, Kutvolgyi Clin Ctr, H-1085 Budapest, Hungary
[3] Semmelweis Univ, Dept Psychiat & Psychotherapy, H-1085 Budapest, Hungary
[4] Eotvos Lorand Univ, Inst Psychol, H-1064 Budapest, Hungary
关键词
copy number variation; structural variants; glycogen synthase kinase 3 beta; major depression; bipolar depression; GSK3B; COPY NUMBER VARIATION; HUMAN GENOME; SCHIZOPHRENIA; DISORDER; ASSOCIATION; POLYMORPHISM; DISEASE; LITHIUM; TARGET; PCR;
D O I
10.1002/ajmg.b.32223
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The glycogen synthase kinase 3B (GSK3B) is an important target protein of several antidepressants, such as lithium, a mood stabilizer. Recent studies associated structural variations of the GSK3B gene to bipolar disorder (BP), although replications were not conclusive. Here we present data on copy number variations (CNVs) of the GSK3B gene probing the 9th exon region in 846 individuals (414 controls, 172 patients with major depressive disorder (MDD) and 260 with BP). A significant accumulation (odds ratio: 5.5, P=0.00051) of the amplified exon 9 region was found in patients (22 out of 432) compared to controls (4 of 414). Analyzing patient subgroups, GSK3B structural variants were found to be risk factors of BP particularly (P=0.00001) with an odds ratio of 8.1 while no such effect was shown in the MDD group. The highest odds (19.7 ratio) for bipolar disorder was observed in females with the amplified exon 9 region. A more detailed analysis of the identified GSK3B CNV by a set of probes covering the GSK3B gene and the adjacent NR1I2 and C3orf15 genes showed that the amplified sequences contained 3 (downstream) segments of the GSK3B and NR1I2 genes but none of them involved the C3orf15 gene. Therefore, the copy number variation of the GSK3B gene could be described as a complex set of structural variants involving partial duplications and deletions, simultaneously. In summary, here we confirmed significant association of the GSK3B CNV and bipolar disorder pointing out that the copy number and extension of the CNV varies among individuals. (c) 2014 Wiley Periodicals, Inc.
引用
收藏
页码:217 / 222
页数:6
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