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

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.