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

• Published in: Viruses 2023-09, Vol.15 (9), p.1898
• Main Authors: Sumala, Sasiwimon, Ekalaksananan, Tipaya, Pientong, Chamsai, Buddhisa, Surachat, Passorn, Supaporn, Duangjit, Sureewan, Janyakhantikul, Somwang, Suktus, Areeya, Bumrungthai, Sureewan
• Format: Article
• Language: English
• Subjects: Biomarkers; Copy number; Cytokines; Deoxyribonucleic acid; DNA; Enzyme-linked immunosorbent assay; Genetic factors; Herpes viruses; HHV-6; Infections; Inflammation; Interleukin 10; Interleukin 6; Lymphocytes; major depressive disorder (MDD); Mental depression; Mental disorders; Mutation; Point mutation; Population; Public health; Questionnaires; Risk factors; Suicide; T cell receptors; TNF-α; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Viral infections
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v15091898

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.