The Association of HHV-6 and the TNF-α (-308G/A) Promotor with Major Depressive Disorder Patients and Healthy Controls in Thailand

Sasiwimon Sumala; Tipaya Ekalaksananan; Chamsai Pientong; Surachat Buddhisa; Supaporn Passorn; Sureewan Duangjit; Somwang Janyakhantikul; Areeya Suktus; Sureewan Bumrungthai

doi:10.3390/v15091898

The Association of HHV-6 and the TNF-α (-308G/A) Promotor with Major Depressive Disorder Patients and Healthy Controls in Thailand

Viruses. 2023 Sep 8;15(9):1898. doi: 10.3390/v15091898.

Authors

Sasiwimon Sumala¹, Tipaya Ekalaksananan^{2

3}, Chamsai Pientong^{2

3}, Surachat Buddhisa⁴, Supaporn Passorn¹, Sureewan Duangjit⁵, Somwang Janyakhantikul⁶, Areeya Suktus^{2

3}, Sureewan Bumrungthai^{3

6

7}

Affiliations

¹ Division of Biotechnology, School of Agriculture and Natural resources, University of Phayao, Phayao 56000, Thailand.
² Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
³ HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand.
⁴ Department of Medical Technology, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand.
⁵ Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani 34190, Thailand.
⁶ Division of Biopharmacy, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani 34190, Thailand.
⁷ Division of Microbiology and Parasitology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand.

Abstract

Major depressive disorder (MDD) is a silent global health problem that can lead to suicide. MDD development is suggested to result from numerous risk factors, including genetic factors. A precise tool for MDD diagnosis is currently not available. Recently, inflammatory processes have been identified as being strongly involved in MDD development and the reactivation of human herpesvirus type 6 (HHV-6), upregulating cytokines such as TNF-α, which are associated with MDD. Therefore, this study aimed to determine the association of HHV-6 with genetic factors, especially TNF-α mutation, in MDD patients and their relatives compared to healthy controls. The Patient Health Questionnaire (PHQ-9) was used to evaluate MDD status, and 471 oral buccal samples were investigated for HHV-6 infection and viral copy number by qPCR. TNF-α (-308G/A) gene mutation and the cytokines TNF-α, IL-6, and IL-10 were analyzed by high-resolution melting (HRM) analysis and enzyme-linked immunosorbent assay (ELISA). Whole-exome sequencing of buccal samples was performed to analyze for genetic factors. The results showed significantly higher HHV-6 positivities and viral loads in MDD patients (15/59 (25.67%) and 14,473 ± 16,948 copies/µL DNA) and their relatives (blood relatives 17/36 (47.22%) and 8146 ± 5656 copies/µL DNA); non-blood relatives 7/16 (43.75%) and 20,721 ± 12,458 copies/µL DNA) compared to the healthy population (51/360 (14.17%) and 6303 ± 5791 copies/µL DNA). The TNF-α (-308G/A) mutation showed no significant difference. Surprisingly, 12/26 (46.15%) participants with the TNF-α (-308G/A) mutation showed HHV-6 positivities at higher rates than those with wild-type TNF-α (-308G) (70/267 (26.22%)). HHV-6-positive participants with TNF-α (-308G/A) showed higher levels of TNF-α, IL-6, and IL-10 than those of negative control. Exome analysis revealed that common mutations in immune genes were associated with depression. Therefore, this study unveiled the novel association of inflammatory gene TNF-α (-308G/A) mutations with HHV-6 reactivation, which could represent a combined risk factor for MDD. This result could induce further research on MDD development and clinical applications.

Keywords: HHV-6; TNF-α; inflammation; major depressive disorder (MDD).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cytokines / genetics
Depressive Disorder, Major* / genetics
Herpesvirus 6, Human* / genetics
Humans
Interleukin-10 / genetics
Interleukin-6 / genetics
Thailand
Tumor Necrosis Factor-alpha / genetics

Substances

Cytokines
Interleukin-10
Interleukin-6
Tumor Necrosis Factor-alpha
TNF protein, human

Grants and funding

This research was funded by the University of Phayao (grant no. FF64-RIB005) and Faculty of Pharmaceutical Sciences, Ubon Ratchathani University (grant no. ภส.อบ.0604.11-5/2566).