Genetic and epigenetic analyses of IFN-γ gene proximal promoter region underlying positive correlation between persistently high anti-SARS-CoV-2 IgG and IFN-γ among COVID-19 vaccinated Bangladeshi adults

• Published in: Vaccine 2024-08, Vol.42 (21), p.126157, Article 126157
• Main Authors: Tahsin, Anika, Bhattacharjee, Piyash, Al Saba, Abdullah, Yasmin, Tahirah, Nabi, A.H.M. Nurun
• Format: Article
• Language: English
• Subjects: 5' Untranslated Regions; Adult; Adults; Anti-SARS-CoV-2 IgG; Antibodies; Antibodies, Viral - blood; Antibodies, Viral - immunology; Bangladesh; Correlation analysis; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 vaccination; COVID-19 vaccines; COVID-19 Vaccines - immunology; Cytokines; DNA methylation; Epigenesis, Genetic; Epigenetics; Evaluation; Female; Gene polymorphism; Gene sequencing; Genetic analysis; Genetic diversity; Genetic polymorphism; Humans; Humoral immunity; IFN-γ; IFN-γ proximal promoter; Immunoglobulin G; Immunoglobulin G - blood; Immunology; Infections; Interferon-gamma - blood; Interferon-gamma - genetics; Interferon-gamma - immunology; Lymphocytes; Male; Middle Aged; mRNA; Nucleotides; Plasma; Plasma levels; Population studies; Promoter Regions, Genetic; Proteins; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; Severe acute respiratory syndrome coronavirus 2; Statistical analysis; Vaccination; Vaccine efficacy; Young Adult; γ-Interferon
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2024.126157

IFN-γ is an immunological modulator influencing IgG isotype and concentration, which present a correlate of protection to evaluate vaccine efficacy. As transiently expressed, stable genetic and epigenetic signatures of the cytokine's expression may exist. This study investigates correlation between plasma IFN-γ and anti-SARS-CoV-2 IgG levels, seeking genetic polymorphisms and epigenetic variations within the IFN-γ gene proximal promoter. 200 COVID-19-vaccinated adults were classified into seropositive and seronegative groups based on plasma anti-SARS-CoV-2 IgG. Upon correlation analysis between anti-SARS-CoV-2 IgG and IFN-γ levels, IFN-γ gene proximal promoter region was subjected to nucleotide sequencing for two subsets: seronegative (21  Q3 and Days post-vaccination >180, n = 24). Relative unmethylation of IFN-γ proximal promoter was assessed for the latter subset and its correlation with plasma IFN-γ and IgG levels was evaluated. A statistically significant positive correlation (r = 0.492, p = 0.018) was observed between IFN-γ and anti-SARS-CoV-2 IgG in the seropositive group with persistently high IgG titre (IgG > Q3, Days elapsed post-vaccination >180). A heterozygous 5’-UTR variant (rs776667149:C>T) identified in one seronegative individual revealed a potential impact on PKR-mediated translational attenuation of IFN-γ mRNA. No significant correlation was found between IFN-γ proximal promoter unmethylation and its plasma levels among HAR individuals with Days post-vaccination of either >180 (r = 0.14, p = 0.679) or