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PLoS One. 2016 Oct 10;11(10):e0164418. doi: 10.1371/journal.pone.0164418. eCollection 2016.

Genome-Wide Association Study Identifies ZNF354C Variants Associated with Depression from Interferon-Based Therapy for Chronic Hepatitis C.

Author information

1
Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
2
Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
3
The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
4
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
5
Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
6
Laboratory for DNA Data Analysis Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics, Mishima, Japan.
7
Department of Psychiatry, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan.
8
Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
9
The Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu, Japan.
10
Third Department of Internal Medicine, Nara Medical University, Kashihara, Japan.
11
Kohnodai Hospital, National Center for Global Health and Medicine, Ichikawa, Japan.
12
Division of Gastroenterology, Department of Medicine, Kurume University, Kurume, Japan.
13
Division of Gastroenterology and Hepatology, Ootakanomori Hospital, Kashiwa, Japan.
14
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
15
Division of Hepatology and Pancreatology, Kawasaki Medical College, Kurashiki, Japan.
16
Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
17
Department of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan.

Abstract

The therapeutic use of interferon (IFN) is known to cause depression that frequently interrupts treatment. To identify genetic variants associated with IFN-induced depression, we conducted a genome-wide association study (GWAS) of 224 Japanese chronic hepatitis C patients receiving IFN-based therapy in a multicenter prospective study and stratified them into two groups according to the Beck Depression Inventory, Second Edition (BDI-II) score. In the GWAS stage, we selected 42 candidate single nucleotide polymorphisms (SNPs) to perform replication analysis in an independent set of 160 subjects. The SNP rs1863918 in strong linkage disequilibrium with SNPs located around the Zinc finger 354C (ZNF354C) gene on chromosome 5 showed a significant association when the results of GWAS and replication were combined (odds ratio = 2.55, P = 7.89×10-8 in the allele frequency model), suggesting that the rs1863918 T allele was associated with IFN-induced depression. Furthermore, logistic regression analysis showed that rs1863918 T allele, a history of depression, and younger age were independent predictive factors for IFN-induced depression. Interestingly, western blotting and immunofluorescence showed that ZNF354C was highly expressed in the hippocampus in mice, a region implicated in the pathology of psychiatric symptoms. In conclusion, we identified rs1863918 as significantly associated with IFN-induced depression, and revealed that the candidate gene ZNF354C is highly expressed in the hippocampus of mice. Our data might be useful for elucidating the pathogenic mechanisms of depression induced by drugs including IFN.

PMID:
27723809
PMCID:
PMC5056723
DOI:
10.1371/journal.pone.0164418
[Indexed for MEDLINE]
Free PMC Article

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