SKG1 expression in response to stress

The environmental stress response in many human tissues is influenced by the Serum and Glucocorticoid-regulated kinase (SKG1) gene. This gene promotes cellular homeostasis under environmental stress, and is involved with sodium homeostasis and cell survival after exposure to UV light and hyperosmolarity, as well as insulin response. A variant (rs9493857) in this gene had allelic frequencies that correlated with latitude and climate in a worldwide population sample, which suggested that natural selection was involved in the differences of the ancestral and variant alleles, and therefore the SKG1 expression, in human populations.
When an environmental stress occurs, a key response in humans is increased systematic glucocorticoid secretion, which causes glucocorticoid receptors (GR) to become activated. GR and Oct1 (a GR cooperating transcription factor) enhance the regulation of GR target genes, such as SKG1. The variant rs9493857 affects the ability of GC-dependent Oct1 to bind at its predicted site, therefore having an effect on the regulation of the expression of SKG1.
The ancestral allele of this gene was determined by comparison to the chimpanzee genomic sequence. This allele was found to be responsible for more efficient binding of the GR-Oct1 complex, and a higher level of SKG1 gene expression in times of environmental stress, than the derived version. Across human populations, the ancestral allele was found to be more frequent in equatorial populations of humans. In figure 1, the ancestral rs9493875 allelic frequencies (black) across 52 populations are shown on a winter maximum temperature map.
An increased expression of SKG1 is also linked with salt-sensitive hypertension and breast and prostate cancers. In African American populations, these diseases have a higher prevalence. These populations also have a higher frequency of the ancestral allele, which suggested that this allele might be involved in increasing the susceptibility of people to these diseases.
By Simone Kefford (s4204905)

Luca F, Kashyap S, Southard C, Zou M, Witonsky D, Di Rienzo A, Conzen SD (2009). ‘Adaptive variation regulates the expression of the human SGK1 gene in response to stress. PLoS Genet vol. 5, no. 5, viewed May 23, 2009, http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000489