Association of HHV‑6 reactivation and SLC6A3 (C>T, rs40184), BDNF (C>T, rs6265), and JARID2 (G>A, rs9383046) single nucleotide polymorphisms in depression

• Published in: Biomedical reports 2024-12, Vol.21 (6), p.181, Article 181
• Main Authors: Bumrungthai, Sureewan, Buddhisa, Surachat, Duangjit, Sureewan, Passorn, Supaporn, Sumala, Sasiwimon, Prakobkaew, Nattaphol
• Format: Article
• Language: English
• Subjects: Age groups; Brain research; Brain-derived neurotrophic factor; Cardiovascular disease; Chromosomes; Complexity; Cytokines; Deoxyribonucleic acid; DNA; DNA methylation; DNA sequencing; Dopamine; Epigenetics; Gene sequencing; Genes; Genetic diversity; Genetic factors; Health risk assessment; Herpes viruses; Infections; Mental depression; Mental disorders; Nucleotides; Patients; Proteins; Public health; Risk factors; Single-nucleotide polymorphism; Software; Viral infections; Whole genome sequencing
• ISSN: 2049-9434; 2049-9442; 2049-9442
• DOI: 10.3892/br.2024.1869

Major depressive disorder (MDD) is a global health concern with a complex etiology involving genetic, environmental and infectious factors. The exact cause of MDD remains unknown. The present study explored the association between genetic factors, human herpesvirus 6 (HHV-6) and MDD. The present study analyzed single nucleotide polymorphisms (SNPs) and HHV-6 viral load in oral buccal samples from patients with MDD (with and without blood relatives with MDD) and healthy controls. The study used high-resolution melt analysis to examine rs40184 (C>T) in the solute carrier family 6 member 3 (SLC6A31) gene, rs6265 (C>T) in the brain-derived neurotrophic factor (BDNF) gene and rs9383046 (G>A) in the jumonji and AT-rich interaction domain-containing 2 (JARID2) gene. HHV-6 infection and viral load was assessed using the quantitative PCR. Whole-exome sequencing was used to examine SNPs. The variant alleles of SNPs rs40184 [18/40 (45.00) vs. 29/238 (12.55%)] and rs6265 [30/54 (55.46) vs. 117/292 (40.06%)] were significantly more common in patients with MDD than in healthy controls, indicating they may be probable hereditary risk factors for MDD. HHV-6 positivity was significantly more common in carriers of the G/A genotype (12/15, 80%) than carriers of the G/G genotype (75/363, 20.7%) for rs9383046, implying that genetic variations may affect HHV-6 risk and MDD onset. Similarly, HHV-6 viral loads were significantly higher in carriers of the G/A genotype (99,990.85±118,392.64 copies/ng DNA) than carriers of the G/G genotype (48,249.30±101,216.28 copies/ng DNA) for rs9383046. Whole-exome sequencing identified two SNPs in JARID2 (rs11757092 and rs9383050) associated with MDD, highlighting its genetic complexity. The present study helps explain the complex interactions between HHV-6 infection, genetics and MDD onset, improving understanding of how SNPs in JARID2 contribute to HHV-6 infection and MDD onset; these findings may impact future approaches to diagnosing and treating MDD.