Abstract
Background/Objectives: Chronic low-grade inflammation drives cardiometabolic risk; functional SNPs may influence individual cytokine and hematologic phenotypes. We investigated genotype-specific relationships between circulating immuno-inflammatory biomarkers and routine blood indices in apparently healthy adults. Methods: In this cross-sectional study, 155 fasting volunteers (26-72 years) were genotyped for IL1RN rs1149222 and TNF-proximal rs2071645. Serum IL-1β, TNF-α, oxidized LDL (oxLDL) and C-reactive protein (CRP) were quantified by ELISA, and complete blood counts were recorded simultaneously. Genotype effects were tested with ANOVA/Kruskal-Wallis; Spearman correlations and age-, sex-, BMI-adjusted linear models explored genotype-stratified associations. Results: Among 155 adults, IL1RN rs1149222 significantly affected IL-1β (TT > TG ≈ GG; ANOVA p = 0.042) and oxLDL (overall p = 0.036), with the clearest difference between heterozygotes and major-allele homozygotes. The same variant produced a modest fall in erythrocyte count and hemoglobin restricted to heterozygotes (RBC p = 0.036; Hb p = 0.041). TNF-proximal rs2071645 strongly raised TNF-α (GG > GA > AA; p < 0.0001) and led to a moderate oxLDL increase, driven by GA versus AA carriers (pairwise p = 0.013), while leaving red-cell indices and CRP unchanged. Baseline leukocyte counts, differentials and derived ratios showed no genotype dependence, and multivariable models revealed no epistatic interaction between the two loci. Conclusions: IL1RN rs1149222 and TNF-related rs2071645 generate two independent inflammatory signatures-an IL-1β-oxidative axis linked to mild erythropoietic suppression and a TNF-lipid axis without hematologic shift. Integrating targeted genotyping with inexpensive hematologic ratios may refine early risk stratification and guide tailored preventive strategies in ostensibly healthy populations.