Magic™ Anti-CAMK2G (Phospho T286) polyclonal antibody

Clinical research in coronary artery disease (CAD) primarily focused on genetic variants located in protein-coding regions. Recently, mutations fall within non-coding regions have been suggested to be essential to the pathogenesis of human complex disease. Super enhancer is a densely spaced cluster of transcriptional enhancers located in non-coding regions, which is critical for regulating cell-type specific gene expression. However, the underlying mechanism of the super enhancer single-nucleotide polymorphisms (SNPs) affecting the risk of CAD remains unclear. By integrating genome-wide association study (GWAS) meta-analysis of CAD and cell/tissue-specific histone modification data set, we identified 366 potential CAD-associated super enhancer SNPs in 67 loci, including 94 SNPs that are involved in regulating chromatin interactive and/ or affecting the transcription factors binding affinity. Interestingly, we found 7 novel functional loci (CBFA2T3, ZMIZ1, DIP2B, SCNN1D/ ACAP3, TMEM105, CAMK2G, and MAPK1) that CAD-associated super enhancer SNPs were clustered into the same or neighboring super enhancers. Pathway analysis showed a significant enrichment in several well-known signaling and regulatory processes, e.g., cAMP signaling pathway and ErbB signaling pathway, which play a key role in CAD metabolism. Our results highlight the potential functional importance of CAD-associated super enhancer SNPs and provide the targets for further insights on the pathogenesis of CAD.

Several lines of evidence suggest that common polygenic variation influences brain function in humans. Combining high-density genetic markers with brain imaging techniques is constricted by the practicalities of collecting sufficiently large brain imaging samples. Pathway analysis promises to leverage knowledge on function of genes to detect recurring signals of moderate effect. We adapt this approach, exploiting the deep information collected on brain function by fMRI methods, to identify molecular pathways containing genetic variants which influence brain activation during a commonly applied experiment based on a face matching task (n = 246) which was developed to study neural processing of faces displaying negative emotions. Genetic markers moderately associated (p<10(-4)) with whole brain activation phenotypes constructed by applying principal components to contrast maps, were tested for pathway enrichment using permutation based methods. The most significant pathways are related to post NMDA receptor activation events, driven by genetic variants in calcium/calmodulin-dependent protein kinase II (CAMK2G, CAMK2D) and a calcium-regulated nucleotide exchange factor (RASGRF2) in which all are activated by intracellular calcium/calmodulin. The most significant effect of the combined polygenic model were localized to the left inferior frontal gyrus (p=1.03 x 10(-9)), a region primarily involved in semantic processing but also involved in processing negative emotions. These findings suggest that pathway analysis of GWAS results derived from principal component analysis of fMRI data is a promising method, to our knowledge, not previously described. (C) 2012 Elsevier Inc. All rights reserved.