Integration of Genomic Information in Development of Pharmacological Vascular Dementia Prevention and Treatment Strategies

Abstract

Treatment of hypertension reduces vascular dementia (VaD) risk but not all anti-hypertensive drugs (AHDs) are equally effective, suggesting drug-gene interactions. To understand this relationship, publicly accessible databases were searched for genes deregulated in VaD and their interactions with AHDs. Genes that were downregulated in association with VaD were MTHFR, SYK, AGT, and RPGRIP1L. Genes that were upregulated in VaD were MMP9 and VEGFA. TNFSF14, AR, and PHLDB2 were also associated with VaD, however, transcription or protein level changes could not be ascertained. Analysis of gene expression data suggests that AHDs differentially regulate VaD-associated genes. Information about AHD up- or downregulation of VaD-associated genes could be used as an empirical basis for the optimal selection of AHDs in clinical trials and, ultimately, for VaD prevention and treatment.