Alternative titles; symbols
HGNC Approved Gene Symbol: FGD6
Cytogenetic location: 12q22 Genomic coordinates (GRCh38): 12:95,076,749-95,217,467 (from NCBI)
Romanoski et al. (2010) reported genetic analysis of thousands of transcript abundance traits in human primary endothelial cell (EC) lines in response to proinflammatory oxidized phospholipids implicated in cardiovascular disease. Of the 59 most regulated transcripts, approximately one-third showed evidence of gene-by-environment (GxE) interaction. The interactions resulted primarily from effects of distal-, trans-acting loci, but a striking example of a local GxE interaction was observed for FGD6. The SNP rs7135847 was associated with expression levels of FGD6 at basal and after oxidative phospholipid treatment. The GxE quantitative trait locus (QTL) at SNP rs7135847 in intron 2 of the FGD6 gene achieved a p value of 9.5 x 10(-22). Both basal and oxidized phospholipid-treated levels were genetically controlled. Cells from individuals with AA genotypes exhibited significantly lower levels of expression than cells with AG or GG genotypes. Upon treatment with oxidized phospholipid, AA cells showed decreased expression, whereas AG or GG cells showed increased expression, representing a striking example of a local gene-by-environment interaction and evidence of a local regulatory element that modifies oxidized phospholipid responsiveness in endothelial cells. Romanoski et al. (2010) suggested that the FGD6 gene harbors an oxidative phospholipid response element, which was not identified given the cloning of the proximal FGD6 promoter from positions -1898 to +224. FGD6 is thought, by sequence homology, to be a Rho family guanine nucleotide exchange factor (RhoGEF) that catalyzes GDP/GTP exchange for small G proteins involved in cytoskeletal pathways.
Romanoski, C. E., Lee, S., Kim, M. J., Ingram-Drake, L., Plaisier, C. L., Yordanova, R., Tilford, C., Guan, B., He, A., Gargalovic, P. S., Kirchgessner, T. G., Berliner, J. A., Lusis, A. J. Systems genetics analysis of gene-by-environment interactions in human cells. Am. J. Hum. Genet. 86: 399-410, 2010. [PubMed: 20170901] [Full Text: https://doi.org/10.1016/j.ajhg.2010.02.002]