Effect of SP110 single nucleotide polymorphisms on expression of selected cytokines in a Ugandan population with pulmonary tuberculosis

The SP110 (speckled protein 110) is a nuclear body protein resulting from the expression of an interferon-stimulated gene crucial for macrophage-mediated killing of Mycobacterium tuberculosis (Mtb), the etiologic agent for human pulmonary tuberculosis (PTB). SP110 single nucleotide polymorphisms (SNPs) have been associated with susceptibility to PTB in different populations. However, the influence of SP110 genetic variants on quantitative host cytokine responses during active PTB remains poorly characterized, particularly in East African populations. We systematically evaluated the association between ten SP110 SNPs and plasma concentrations of six key immunoregulatory cytokines, IL-4, IL-6, IL-10, IFN-γ, TNF, and IFN-α, among bacteriologically confirmed PTB patients in Kampala, Uganda. We conducted a cross-sectional molecular epidemiological study among 153 adults with bacteriologically confirmed PTB recruited from Mulago National Referral Hospital and Kisenyi Health Centre IV, Kampala, Uganda. SP110 SNP genotyping was performed using a validated mass array protocol. Plasma cytokine concentrations were quantified by Luminex multiplex bead-based immunoassay and log₂-transformed before analysis. Genotype–phenotype associations were evaluated under additive, dominant, and recessive genetic inheritance models using multivariable generalized linear models adjusted for age, sex, HIV status, TB treatment status, and BCG vaccination scar. Multiple testing was controlled using the Benjamini–Hochberg false discovery rate (FDR) procedure. Multivariate immune profiling was conducted using Spearman correlation matrices and principal component analysis (PCA). Eight of the ten SP110 SNPs satisfied Hardy Weinberg Equilibrium (HWE), while rs11556887 and rs1427294 were near-monomorphic among the participants. All six cytokines were strongly intercorrelated (Spearman ρ = 0.38–0.85, all p < 0.001), and PCA demonstrated that a single dominant principal component, driven by IL-4, IFN-γ, TNF, IFN-α, and IL-10, explained 76.6% of inter-individual cytokine variance, reflecting a coordinated innate-adaptive immune response. One association survived Benjamini–Hochberg FDR correction: rs7580900 was significantly associated with IL-10 (β = − 2.02, 95% CI: − 3.03 to − 1.02, p < 0.001, FDR q = 0.019). Additional nominally significant associations ( p < 0.05) were observed for rs2241525 and rs3948464 with IL-6 and IL-10 and for rs7580900 and rs3948464 with IFN-γ, though none of these secondary associations survived FDR correction. We report a significant association of SP110 rs7580900 with reduced IL-10 plasma concentrations among Ugandan PTB patients, implicating this variant in the modulation of anti-inflammatory regulatory responses during active Mtb infection. The strong cytokine co-expression profile observed across suggests a coordinated nature of the PTB immune response. The identified immune network structure supports the development of host-directed therapeutic strategies targeting cytokine regulation. Genetic screening of key regulatory variants such as SP110 rs7580900 may also contribute to innovative precision medicine approaches for tuberculosis management.