| Notes
|
This gene encodes apolipoprotein (apo-) A-II, which is the second most abundant protein of the high density lipoprotein particles. The protein is found in plasma as a monomer, homodimer, or heterodimer with apolipoprotein D. Defects in this gene may result in apolipoprotein A-II deficiency or hypercholesterolemia. Analysis of trancription factors that bind response elements in the apoA-II promotor and modulate transcription. Carriers of a novel splice-site mutation in the LDL-receptor gene were simultaneously homozygous for the -265C variant of apoA-II thus concluding that one variant of the apoA-II gene was associated with reduced plasma LDL cholesterol in FH patients. Crystallographic studies of apo A-II and its complex with lipid surrogate beta-octyl glucoside show that disulfide-linked dimers of apo A-II form amphipathic alpha-helices which aggregate into tetramers. Evaluated as a positional candidate gene for familial Type II diabetes, altered lipid concentrations, and insulin resistance. Genetic association of plasma apolipoprotein A-II levels with familial combined hyperlipidemia. In transgenic mice overexpressing the human apoA-II gene, plasma human apoA-II concentration was positively correlated with blood glucose levels. NDRG1 interacts with APO A-I and A-II and may have a role in the general mechanisms of HDL-mediated cholesterol transport. Overexpressed human apoA-II in mice impairs HDL protection of apoB-lipoproteins from oxidation. Displacement of PON1 by apoA-II may explain why PON1 is found in HDL particles with apoA-I, not apoA-II, & apo-A-II-rich HDL's poor antiatherogenic properties. Overexpression in transgenic mice does not increase their susceptibility to insulin resistance and obesity. Results show that during the early stages, oxidation of HDL gives rise to specifically oxidized forms of apolipoproteins A-I and A-II. This protein inhibits high density lipoprotein remodeling and lipid-poor apolipoprotein A-I formation. ApoA-II affects both the structure and the dynamic behavior of HDL particles and selectively modifies lipid metabolism. Apolipoproteins appear to be a class of mediators that can participate in the regulation of the activity of neutrophils. Results indicate a significant association between the T265C APOA-II polymorphism and levels of visceral adipose tissue in premenopausal women present in white but not African-American women. This protein-exonic splicing enhancer interaction is able to promote the incorporation of exon 3 in mRNA and suggest that they can rescue the splicing despite the noncanonical 3' splice site. When expressed in transgenic mice, HDL shows antioxidant properties.
|