Abstract Thu159: Sex-specific differences in transcriptomic profile in black individuals to predict cardiovascular health

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Background: Cardiovascular diseases (CVD) are the leading cause of mortality, disproportionately affecting Black individuals compared to other racial groups. Over 60% of adult Black females have some form of CVD. The American Heart Association’s Life’s Simple 7 (LS7) is a standardized measure of cardiovascular health (CVH), evaluating seven key clinical domains. This study utilizes RNA sequencing (RNAseq) of blood samples to investigate transcriptomic differences in differentially expressed genes (DEGs) among Black individuals residing in the Atlanta metropolitan area. Methods: This cross-sectional study analyzed RNAseq data from whole blood samples (PAXgene) collected from 373 Black individuals aged 30 and older. CVH was assessed using LS7 scores, derived from standardized questionnaires and clinical measurements. Differential gene expression analysis was performed using limma, ranking individuals into high and low LS7 groups. Gene set enrichment analysis (GSEA) identified biological pathways enriched among DEGs. Results: In females, glucose levels and blood pressure were the strongest correlates of LS7 scores, while in males, blood pressure, cholesterol, and glucose had the highest correlation. DEG analysis identified 520 upregulated and 272 downregulated genes associated with high LS7 scores (ideal CVH) in females, whereas 214 upregulated and 210 downregulated genes were significantly differentially expressed in males (adj. p < 0.05). Fold changes ranged from 0.35 to 2.73 in females and from 0.46 to 3.99 in males. Notably, VCAN and SORL1 were upregulated in both males and females with high LS7 scores. Mitochondrial DEGs were more prevalent in males (13.2%, n = 56) than in females (9.6%, n = 76). Among oxidative phosphorylation (OXPHOS)-related genes, males had a slightly higher proportion of DEGs in Complexes II and III (12%, n = 2) compared to females (8%, n = 2), while females had more DEGs in Complex V (17%, n = 4) than males (6%, n = 1). Conclusions: This study highlights sex-specific transcriptomic differences in Black individuals, identifying key genes and pathways linked to cardiovascular health. These findings underscore the potential of RNAseq analysis in addressing cardiovascular health disparities in this population.

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