PNPLA3 and liver disorder: Although polymorphisms in both PNPLA3 and TM6SF2 (i.e. PNPLA3 rs738409 c.444 C > G p.I148M and TM6SF2 rs58542926 C > T E167K) are well known to be associated with more severe liver disease, these polymorphisms in both genes act to decrease VLDL levels and thereby potentially protect the vasculature from the normal increase in atherogenic VLDL and the development of the atherogenic lipoprotein phenotype that would normally occur in patients with NAFLD.