Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic basis for vascular dementia (VD) as a typical complex disease has been limitedly reported from association studies conducted with candidate genes. Even recent genomewide association studies (GWAS) could hardly identify additional genetic factors for VD. Although a considerable complexity for its genetic architecture was suspected, there were some challenges to identify false negative associations that resulted from the GWAS. Challenges to identifying genetic factors and their functions after the trials of GWAS revealed that splicing of primary transcript was inhibited (SYK) or delayed (PHLDB2) by a nucleotide substitution of the corresponding gene. The studies gave us the lesson that integrated investigations with statistical genomics as well as functional genomics are needed to identify false negatives from the GWAS. Such endeavors would provide key insights into aspects of underlying nucleotide architectures of VD and incorporate the genetic factors into clinical practice. The recent genetic association studies for susceptibility to VD were briefly overviewed in this article. We also showed a challenge to understanding genetic dissection of VD by a genomic region enrichment analysis with distal cis-regulatory sequences. The analysis with a variant set of potential false negatives from the GWAS revealed that the variants were significantly enriched near genes involved in critical biological processes to VD.
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PMID:Complex genetic susceptibility to vascular dementia and an evidence for its underlying genetic factors associated with memory and associative learning. 2326 36

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.
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PMID:Integration of genomic information in development of pharmacological vascular dementia prevention and treatment strategies. 2502 8