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

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2023 Sep 28

PMID 37766304

Authors

Sasiwimon Sumala

Tipaya Ekalaksananan

Chamsai Pientong

Surachat Buddhisa

Supaporn Passorn

Sureewan Duangjit

Somwang Janyakhantikul

Areeya Suktus

Sureewan Bumrungthai

Affiliations

Soon will be listed here.

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-, which are associated with MDD. Therefore, this study aimed to determine the association of HHV-6 with genetic factors, especially 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. (-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 (-308G/A) mutation showed no significant difference. Surprisingly, 12/26 (46.15%) participants with the (-308G/A) mutation showed HHV-6 positivities at higher rates than those with wild-type (-308G) (70/267 (26.22%)). HHV-6-positive participants with (-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 (-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.

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