Disease relevance of APOA2

• Microsatellite DNA assays reveal an allelic imbalance in p16(Ink4), GALT, p53, and APOA2 loci in patients with endometriosis [1].
• A novel beneficial role for apolipoprotein A-II in the pathogenesis of hepatitis C virus has been shown [2].
• The primary translation product of human apolipoprotein A-II was purified from wheat germ and ascites cell-free lysates programmed with RNA isolated from either a hepatocellular carcinoma cell line (HepG2) or intestinal epithelium [3].
• Overexpression of human apolipoprotein A-II in transgenic mice does not increase their susceptibility to insulin resistance and obesity [4].
• As apoA-II-deficient mice present a phenotype of insulin hypersensitivity, a function of apoA-II in regulating FFA metabolism seems likely [5].

Psychiatry related information on APOA2

• As compared to sucrose, alcohol consumption was associated with a significant elevation in serum apolipoprotein A-I (0.37 mg/dl/g/day of alcohol) with similar effects for serum HDL cholesterol (0.14 mg/dl/g/day of alcohol) and serum apolipoprotein A-II (0.11 mg/dl/g/day of alcohol) achieving borderline levels of statistical significance [6].
• Serum apolipoprotein A-II, a biochemical indicator of alcohol abuse [7].
• The serum apolipoprotein A II may involve the pathological process in the patients with senile dementia [8].

High impact information on APOA2

• Physical positioning of known genes in the area (APOA2 and three selectin genes) outside the linked region suggests a novel locus for FCHL on 1q21-q23 [9].
• One marker, D1S104, adjacent to the apolipoprotein A-II (APOA2) gene on chromosome 1, revealed a lod score of Z = 3.50 assuming a dominant mode of inheritance [9].
• Levels of apolipoprotein A-I and apolipoprotein A-II were also associated with decreased risk [10].
• Apolipoprotein AIV and apolipoprotein E concentrations were comparable to those in controls, and apolipoprotein AII was considerably decreased [11].
• Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor [12].

Chemical compound and disease context of APOA2

• Human ApoA-II inhibits the hydrolysis of HDL triglyceride and the decrease of HDL size induced by hypertriglyceridemia and cholesteryl ester transfer protein in transgenic mice [13].
• Opposite effects of plasma from human apolipoprotein A-II transgenic mice on cholesterol efflux from J774 macrophages and Fu5AH hepatoma cells [14].

Biological context of APOA2

• NEM1 was assigned to chromosome 1 by close linkage for APOA2, which is localized to 1q21-q23 [15].
• NEM1 was assigned to chromosome 1 by close linkage to APOA2, with a lod score of 3.8 at a recombination fraction of 0 [15].
• A candidate gene study in low HDL-cholesterol families provides evidence for the involvement of the APOA2 gene and the APOA1C3A4 gene cluster [16].
• CONCLUSION(S): We found that loss of heterozygosity on p16(Ink4), GALT, and p53, as well as on APOA2, a region frequently lost in ovarian cancer, occurs in endometriosis, even in stage II of the disease [1].
• Apolipoprotein A-II: beyond genetic associations with lipid disorders and insulin resistance [2].

Anatomical context of APOA2

• To determine the apolipoprotein specificity of high density lipoprotein (HDL) receptor, apolipoprotein A-I (apo-AI) and apolipoprotein A-II (apo-AII) purified from high density lipoprotein3 (HDL3) were reconstituted into dimyristoyl phosphatidylcholine vesicles (DMPC) and their ability to bind to luteinized rat ovarian membranes was examined [17].
• Whereas nontransgenic HDL protected against oxidized LDL induction of adhesion molecules in endothelial cells, HDL from apoA-II transgenic mice was proinflammatory [18].
• The macrophage-to-smooth muscle cell ratio of lesions was 2.1-fold higher in apo-I/apoA-II mice than in apoA-I mice (P<0.01) [19].
• ApoAII gene expression was demonstrated in adult human liver and HepG2 cells but not in human small intestine [20].
• To determine the association between the -265 T to C substitution in the apolipoprotein A-II (APOA-II) gene and levels of visceral adipose tissue (VAT) in a group of premenopausal African-American and white women, we genotyped 237 women (115 African-American and 122 white) for this polymorphism [21].

Associations of APOA2 with chemical compounds

• Human and murine apolipoprotein A-II differently affect glucose metabolism and insulin resistance [2].
• Purified human apoA-II was incorporated into sonicated, spherical LpA-I particles containing apoA-I, phospholipids, and various amounts of triacylglycerol (TG), diacylglycerol (DG), and/or free cholesterol [22].
• Human apolipoprotein A-II associates with triglyceride-rich lipoproteins in plasma and impairs their catabolism [23].
• ApoA-II isolated from human plasma high density lipoprotein (HDL) by column chromatography migrated as a single band on polyacrylamide disc gel electrophoresis, had the appropriate amino acid composition, and provoked the production of monospecific antisera [24].
• In assays, (0.05 M barbital buffer, 0.01% Triton X-100, pH 8.6) over 90% of (125)I-ApoA-II was bound by excess first antibody and over 95% was displaced by excess "cold" ApoA-II [24].

Physical interactions of APOA2

• We have also found that the (GU) repeats in the apoA-II context bind the splicing factor TDP-43 and interfere with exon 3 definition [25].

Regulatory relationships of APOA2

• Apolipoprotein A-II inhibits high density lipoprotein remodeling and lipid-poor apolipoprotein A-I formation [26].
• In addition, apoA-II enhances the ability of reconstituted LpA-I particles to inhibit VLDL-TG hydrolysis by HL [22].
• However, when the same amounts (0.1-3.0 nmol/assay) of apo A-II were incorporated together with apo A-I (0.8 nmol/assay) into the liposome, apo A-II significantly stimulated LCAT activity as compared to activity obtained with incorporation of apo A-I alone [27].

Other interactions of APOA2

• Multipoint analysis between VP, SPTA1, APOA2 and D1S194 gave the maximum LOD score of 6.62 at APOA2, which has been physically mapped to 1q21-q23 [28].
• CETP remodeled approximately 32% (A-I/A-II)rHDL into small but not large particles [26].
• We used linkage analysis with polymorphic CA repeats to test for the involvement of two candidate loci, APOA2 and ACTN2 [29].
• The average normolipidemic concentration of ApoA-I associated with ApoA-II in 50 women was 790 mg/L; in 50 men, it was 788 mg/L [30].
• The apolipoprotein profile of all patient groups was characterized by significantly reduced levels of apolipoprotein (Apo)A-I and ApoA-II and significantly increased levels of ApoC-III [31].

Analytical, diagnostic and therapeutic context of APOA2

• A double antibody radioimmunoassay for human ApoA-II is reported [24].
• We produced a monoclonal antibody (C2-22) to human apolipoprotein (Apo) AII and describe its use in an enzyme-linked immunoabsorbant assay (ELISA) for Apo AII in human plasma and lipoprotein subfractions [32].
• RT-PCR products for Apos C-I, C-II, E, and J were found in retina and RPE; for ApoA-II in the retina only [33].
• Drinking habits influence the relationship between apolipoprotein AII and body mass index [34].
• We screened the apolipoprotein A-II gene by single strand conformation polymorphism analysis and fluorescent sequence analysis [35].

References