Association between TNF-α (-308G > A) promoter polymorphism and HHV-6 DNA detection in a community-based Thai cohort.

Authors

Sureewan Bumrungthai, Sutida Pongpukdeesakul, Tipaya Ekalaksananan, Sureewan Duangjit, Chamsai Pientong, Nuchsupha Sunthamala

Published in

Frontiers in microbiology. Volume 17. Pages 1825548. Epub Jun 17, 2026.

Abstract

Human herpesvirus 6 (HHV-6) establishes lifelong latency after primary infection and may reactivate under conditions of immune modulation. Tumor necrosis factor alpha (TNF-α) is a key pro-inflammatory cytokine involved in antiviral responses, and functional variation in the TNF-α promoter (-308G > A, rs1800629) may influence host-virus equilibrium. However, population-based data examining host genetic determinants of HHV-6 detection in Southeast Asia remain limited.
We conducted a community-based cross-sectional study of 852 participants aged 3-90 years in Phayao Province, Thailand. HHV-6 DNA was detected by nested PCR and quantitative PCR. Genotyping of TNF-α (rs1800629) and additional polymorphisms was performed using high-resolution melt analysis with sequencing validation. Sociodemographic, clinical, and psychological variables were assessed using standardized questionnaires. Multivariable logistic regression was used to evaluate independent predictors of HHV-6 positivity.
HHV-6 DNA was detected in 12.8% of participants and increased with age (adjusted OR per 10-year increase 1.55, 95% CI 1.35-1.78; p < 0.001). The TNF-α (-308G > A) polymorphism was independently associated with HHV-6 detection (adjusted OR 3.21, 95% CI 1.98-5.20; p < 0.001). Lower education level also remained significant (adjusted OR 3.88, 95% CI 1.35-11.15; p = 0.012). The DAT1 (rs40184) genotype showed a modest association in the full model (adjusted OR 1.84, 95% CI 1.02-3.32; p = 0.041) but was borderline in adult-only sensitivity analysis. Psychological measures were not independently associated with HHV-6 positivity.
In this Thai community cohort, the TNF-α (-308G > A) promoter variant was independently associated with HHV-6 DNA detection. These findings support an observational model in which host immunogenetic variation contributes to inter-individual differences in viral DNA detection, although longitudinal studies are required to clarify causal mechanisms.

PMID:
42388306
Bibliographic data and abstract were imported from PubMed on 02 Jul 2026.

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