Atf6 emerged as another candidate gene in the proximal Chr 1 QTL interval. Here, one is actually referring to Atf6α, which is distinct from Atf6β (Hai and Hartman 2001; Thuerauf et al. 2007). For Atf6α, two non-synonymous coding SNPs with the appropriate haplotype structure were confirmed. One of these, H77P occurs in the N-terminus region known to be key for transcriptional activation and proteasomal degradation (Thuerauf et al. 2007). ATF6α is a 670-amino-acid transmembrane endoplasmic reticulum (ER) protein that is cleaved in response to ER stress; the cytoplasmic fragment is translocated to the nucleus where it activates the expression of a variety of genes, some of which are involved in the unfolded protein response (UPR). Chen et al. (2008) have shown that under in vitro conditions in both SH-SY5Y neuroblastoma cells and primary cerebellar cultures, ethanol can markedly potentiate the ER stress response induced by tunicamycin or thapsigargin; the mechanism of this ethanol effect appears to involve the production of reactive oxygen species. It also should be noted that, in addition to UPR-associated genes, ATF6α also regulates the expression of
