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. 2024 Oct 3;21(6):181.
doi: 10.3892/br.2024.1869. eCollection 2024 Dec.

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

Sureewan Bumrungthai  1   2 , Surachat Buddhisa  3 , Sureewan Duangjit  4 , Supaporn Passorn  5 , Sasiwimon Sumala  5 , Nattaphol Prakobkaew  3
Affiliations

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

Sureewan Bumrungthai et al. Biomed Rep. .

Abstract

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.

Keywords: brain-derived neurotrophic factor; human herpesvirus 6; jumonji and AT-rich interaction domain-containing 2; major depressive disorder; single nucleotide polymorphism; solute carrier family 6 member 3.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Association between HHV-6 infection and JARID2 rs9383046. HHV-6, human herpes virus 6; JARID2, jumonji and AT-rich interaction domain containing 2.
Figure 2
Figure 2
HHV-6 viral load in individuals with polymorphism of SLC6A3, BDNF and JARID2. HHV-6, Human herpes virus 6; SLC6A3, Solute carrier family 6 member 3; BDNF, brain-derived neurotrophic factor; and JARID2, jumonji and AT-rich interaction domain containing 2.
Figure 3
Figure 3
Association between single nucleotide polymorphisms in JARID2 and associated pathways. JARID2, jumonji and AT-rich interaction domain containing, 2; MDD, major depressive disorder; RS, Reference SNP.
See this image and copyright information in PMC

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