JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE) ›› 2021, Vol. 41 ›› Issue (10): 1303-1307.doi: 10.3969/j.issn.1674-8115.2021.10.005

• Clinical research • Previous Articles     Next Articles

Association study of CREB1 gene with depression and bipolar disorder typeⅡ

Bo SHI1(), Jian-min CHEN1, Jun-xiong ZHAO1, Wei TANG2, Wei-xing FAN1, Cheng-cheng ZHANG3, Chen ZHANG4()   

  1. 1.Department of Psychiatry, Jinhua Second Hospital, Jinhua, Zhejiang 321016, China
    2.Department of Psychiatry, The Affiliated Kangning Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 32500, China
    3.Department of Psychiatry, Yuebei Third People's Hospital, Shaoguan, Guangdong 512200, China
    4.Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
  • Online:2021-10-28 Published:2021-09-22
  • Contact: Chen ZHANG E-mail:shibojinhua@163.com;zhangchen645@gmail.com
  • Supported by:
    National Key Research and Development Plan(2018YFC1314300);National Natural Science Foundation of China(81771450);Project of Science and Technology Bureau of Jinhua(2015-3-063)

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Abstract: Objective

·To study the association of CREB1 gene with depression and bipolar disorder type Ⅱ.

Methods

·Three hundred and sixty-two patients with depression, 381 patients with bipolar disorder type Ⅱ and 416 healthy subjects were included. There were no significant differences in gender, age and year of education between depression group, bipolar disorder type Ⅱ group and control group. Patients with severity of depression were evaluated by Hamilton Depression Rating Scale. Hypomania Check List-32 was used to screen the history of hypomanic episode of patients with depression and patients with bipolar disorder type Ⅱ. A total of 2 mL of venous blood was collected from each subject, and whole genome of peripheral blood leukocyte DNA was extracted using a centrifugal column genomic DNA kit. Single nucleotide polymorphism (SNP) genotyping of SNaPshot was used to identify the rs10932201 and rs3770704 loci of CREB1 gene, and the effects of SNP on CREB1 expression in brain were analyzed using BRAINEAC database.

Results

·The genotypes of rs10932201 and rs3770704 of CREB1 gene in the depression group, bipolar disorder type Ⅱ group and control group were well matched with Hardy-Weinberg equilibrium (P>0.05). Linkage disequilibrium analysis showed that there was a strong linkage disequilibrium between rs10932201 and rs3770704 (r2>0.4). At the rs10932201 locus of CREB1 gene, there was a significant difference in allelic frequency between the bipolar disorder type Ⅱ group and the control group (χ2=4.27, P=0.042); there was no difference in allelic frequency between the depression group and the control group. There were no significant differences in either allelic or genotypic frequency of rs3770704 of CREB1 gene in the depression group and bipolar disorder type Ⅱ group compared with the control group. In the haplotype constructed between rs10932201 and rs3770704 of CREB1 gene, the frequency of haplotype A-T in the bipolar disorder type Ⅱ group was 57.5%, which was statistically significant (χ2=4.07,P=0.044). Expression quantitative trait loci analysis showed that rs10932201 was associated with CREB1 gene expression in temporal cortex (P=0.048).

Conclusion

·The rs10932201 of CREB1 gene is associated with bipolar disorder type Ⅱ, and may be a risk factor for bipolar disorder type Ⅱ, not depression.

Key words: CREB1 gene, depression, bipolar disorder type Ⅱ, polymorphism, expression quantitative trait loci

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