Influence of IL10 promoter variants rs1800896 (-1082 A > G), rs1800871 (-819 C > T), and rs1800872 (-592 C > A) and haplotypes on COVID-19 symptom presentation in outpatients from Western Mexico

Abstract Background/Objectives Interleukin-10 (IL-10) is a key immunoregulatory cytokine whose expression is influenced by genetic variation within its promoter region. Altered circulating IL-10 levels have been associated with COVID-19, highlighting its relevance in modulating host immune responses during SARS-CoV-2 infection. This study aimed to evaluate the association of IL10 promoter variants rs1800896 (−1082 A > G), rs1800871 (−819 C > T), and rs1800872 (−592 C > A), haplotypes, and circulating IL-10 concentrations with the clinical presentation of COVID-19 in Mexican outpatients. Methods A case–control study was conducted in 179 Mexican outpatients with confirmed SARS-CoV-2 infection, including symptomatic cases and asymptomatic controls. IL10 promoter variants (rs1800896A>G, rs1800871C>T, and rs1800872C>A) were genotyped using PCR-RFLP, and serum IL-10 levels were quantified by ELISA. Haplotype analyses were estimated, and their associations with clinical symptoms were assessed. Results No significant differences in genotypic or allelic frequencies of rs1800896A>G or rs1800871C>T were observed between symptomatic and asymptomatic individuals. In contrast, the rs1800872C>A genotype (codominant model) and the combined CA+AA genotypes (dominant model) were significantly more frequent among asymptomatic participants, conferring protection against symptomatic infection (aOR = 0.52; 95% CI: 0.28–0.97). Haplotype analysis revealed a higher frequency of the ACC haplotype in symptomatic patients (aOR = 1.68; 95% CI: 1.01–2.79), who also exhibited higher circulating IL-10 levels than GCC carriers (1.018 vs 0.564 pg/mL). Although overall IL-10 concentrations did not differ significantly between groups, elevated levels were observed in individuals reporting anosmia (1.026 vs 0.515 pg/mL) and ageusia (1.186 vs 0.606 pg/mL), whereas lower levels were detected in those with pharyngitis (0.59 vs 0.939 pg/mL). Conclusions Variability in the IL10 promoter particularly the rs1800872 C>A variant and the ACC haplotype, was associated with symptom presentation and with haplotype-specific circulating IL-10 levels during SARS-CoV-2 infection.