1535-P: Gene Expression and Pathway Analysis in African Americans with T2DM and HCV Comorbidity

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Introduction and Objective: Hepatitis C Virus (HCV) infection and type 2 diabetes mellitus (T2DM) are critical health challenges disproportionately affecting African Americans (AAs), who exhibit the highest prevalence in the U.S. This study is an integrative approach to finding molecular and genetic signatures of perturbed metabolic and mechanistic pathways in T2DM with HCV in an AAs from Washington, DC area. Methods: A total of 45 AA patients were recruited from the Howard University Hospital and categorized as T2DM only (n=23), HCV only (n=11), and T2DM+HCV (n=11), along with 17 controls. Whole blood RNA sequencing was performed using Illumina technology, followed by Ingenuity Pathway Analysis (IPA) to identify pathways and biofunctions. Results: In the T2DM+HCV group, 752 genes were differentially expressed, with 97 genes commonly altered across all disease groups. IFNA2, STAT1, NONO, and IFNAR1 were significantly activated, while ETV3 showed inhibition. IPA highlighted Interferon alpha/beta signaling, Neutrophil degranulation, and IL-27 signaling as top canonical pathways (p<0.05), associated with viral replication, phagocyte movement, and infection. Conclusion: This study provides insights into dysregulated genes and pathways in AAs with T2DM and how HCV infection may contribute to the progression of T2DM, and identify potential avenues for treatment and prevention, in this minority AA population. Disclosure T. Mondal: None. C. Loffredo: None. R. Quartey: None. G. Moses: None. C. Howell: None. B.E. Korba: None. G. Nunlee-Bland: None. Z. Noreen: None. J. Sahota: None. J. Simhadri: None. M. Lemma: None. S. Ghosh: None. Funding National Institutes of Health (5U54MD007597-35)

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