IRS1 and Insulin resistance: IRS1 rs1801278 is a missense polymorphism that decreases the phosphorylation of IRS-1 in vitro (McGettrick et al., 2005), reducing the binding of p85 to IRS-1 and the activity of PI3K in different cell lines (Hribal et al., 2000; Sentinelli et al., 2006), and leading to insulin resistance.