SAT-278 Novel Sexual Dimorphic Lipid Relationship with IL18 in African Americans

Abstract Disclosure: U.B. Ogbuehi: None. K. Webb: None. A. Gayle: None. R. Kittles: None. J. Johnson: None. L. Woods-Burnham: None. K.S. Kimbro: None. Novel Sexual Dimorphic Lipid Relationship with IL18 in African AmericansBackground/Significance: IL-18 plays a role in the regulation of multiple cytokines, which are associated with multiple cardiometabolic disorders. However, the interaction between IL-18 and other factors closely related to lipid metabolism, particularly regarding sexual dimorphism, remains underexplored. While sex differences in lipid metabolism, salt absorption, and cholesterol levels have been noted, their manifestation across sexes in African Americans is understudied. We hypothesize that cholesterol serum level profiles distinct sex-specific patterns, possibly offering insights into cardiometabolic disease mechanisms and lipid metabolism response differences across sexes. Methods: Blood samples from 190 males and 369 females aged 40 to 92 were collected as part of the Discovery of Us™ Project. The cohort was divided into two groups based on IL-18 levels. Cytokine expression was quantified using Mean Fluorescence Intensity (MFI) from high-sensitivity multiplex assays on the xMAP Intelliflex DRO platform. Data was analyzed using linear regression and T-tests. Results: Analysis showed significant correlations between IL-18 levels and cholesterol, LDL, HDL, and VLDL. In females, the low IL-18 group exhibited strong positive correlations with VLDL (R = 0.1663, p = 0.0312) and triglycerides (R = 0.1650, p = 0.0326); no significance was observed in males, suggesting a sex difference in the relationship with IL18. The most significant inverse correlation was seen with CRP in the high IL-18 group (R = -0.7075, p = 0.0330), indicating a strong link between inflammation and IL-18 in females. Total cholesterol and LDL also showed moderate negative correlations in both IL-18 groups. Furthermore, VLDL and triglycerides also showed substantial positive associations. In the high IL-18 group, the inflammatory marker CRP exhibited a strong correlation (R = 0.9663, p = 0.0017), in contrast to the negative correlation seen only in females. Additionally, total cholesterol, LDL, and HDL displayed stronger negative associations in males than females but not significant. Conclusions: These findings suggest novel insights that males with low IL-18 are more strongly linked to metabolic markers, whereas females with high IL-18 show a more significant inflammatory response. The sex-specific differences in metabolic profiles in African American populations may influence cardiometabolic disease prevalence and severity. Acknowledgment of funding: •This research is partly supported by grant numbers U54MD007602 and R01MD017405 from the National Institutes of Health. Presentation: Saturday, July 12, 2025