Down-regulation of PRKCB1 expression in Han Chinese patients with subsyndromal symptomatic depression.
BACKGROUND
Subsyndromal symptomatic depression (SSD) is a common disease with significant social dysfunction. However, SSD is still not well understood and the pathophysiology of it remains unclear.


METHODS
We classified 48 candidate genes for SSD according to our previous study into clusters and pathways using DAVID Bioinformatics Functional Annotation Tool. We further replicated the result by using real-time Quantitative PCR (qPCR) studies to examine the expression of identified genes (i.e., STAT5b, PKCB1, ABL1 and NRAS) in another group of Han Chinese patients with SSD (n = 50). We further validated the result by examining PRKCB1 expression collected from MDD patients (n = 20). To test whether a deficit in PRKCB1 expression leads to dysregulation in PRKCB1 dependent transcript networks, we tested mRNA expression levels for the remaining 44 genes out of 48 genes in SSD patients. Finally, the power of discovery was improved by incorporating information from Quantitative Trait (eQTL) analysis.


RESULTS
The results showed that the PRCKB1 gene expression in peripheral blood mononuclear cells (PBMC) was 33.3% down-regulated in SSD patients (n = 48, t = 3.202, p = 0.002), and a more dramatic (n = 17, 49%) down-regulation in MDD patients than control (n = 49, t = 2.114, p = 0.001). We also identified 37 genes that displayed a strong correlation with PRKCB1 mRNA expression levels in SSD patients. The expression of PRKCB1 was regulated by multiple single nucleotide polymorphisms (SNPs) both at the transcript level and exon level.


CONCLUSIONS
In conclusion, we first found a significant decrease of PRCKB1 mRNA expression in SSD, suggesting PRKCB1 might be the candidate gene and biomarker for SSD.
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06511, United States; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, United States.
Xiaoyun
X
Guo
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zezhi
Z
Li
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chen
C
Zhang
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhenghui
Z
Yi
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Haozhe
H
Li
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Lan
L
Cao
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chengmei
C
Yuan
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wu
W
Hong
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhiguo
Z
Wu
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Daihui
D
Peng
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jun
J
Chen
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Weiping
W
Xia
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Guoqing
G
Zhao
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Fan
F
Wang
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shunying
S
Yu
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Donghong
D
Cui
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yifeng
Y
Xu
Magnetic Resonance Research Center, Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, United States.
Chowdhury M I
CM
Golam
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 101 Woodruff Circle, Suite 4000, Atlanta, GA 30322, United States.
Alicia K
AK
Smith
Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06511, United States.
Tong
T
Wang
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: yirufang@gmail.com.
Yiru
Y
Fang
D000328:Adult; D044466:Asian People / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D002681:China; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D003863:Depression / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000208:ethnology / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D064546:Protein Kinase C beta / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D012984:Software
D015415:Biomarkers; D012333:RNA, Messenger; C579054:PRKCB protein, human; D064546:Protein Kinase C beta
ERBB signal pathway; Gene expression; Major depressive disorder; PRKCB1; Subsyndromal symptomatic depression