PCSK9 and coronary artery disorder: Several other interactions also suggest a role for immune response and inflammation in the development of leukoaraiosis including gene-environment interactions between IL28RA (class II cytokine receptor) and small dense LDL size, IL22RA1 (class II cytokine receptor) and coronary heart disease, and both LTA4H (leukotriene hydroxylase) and PCSK9 (which plays a role in LDL receptor degradation) and homocysteine.