Disease relevance of APOC1

• In addition, we have isolated a single lambda phage carrying both APOC1 and part of APOE [1].
• Exact localization of the familial dysbetalipoproteinemia associated HpaI restriction site in the promoter region of the APOC1 gene [2].
• Obese obob mice with strong overexpression of the human apolipoprotein C1 (APOC1) exhibit excessive free fatty acid (FFA) and triglyceride (TG) levels and severely reduced body weight (due to the absence of subcutaneous adipose tissue) and skin abnormalities [3].
• Severe hypertriglyceridemia in human APOC1 transgenic mice is caused by apoC-I-induced inhibition of LPL [4].
• Commonly up-regulated genes in gastric cancer in comparison with normal gastric epithelia included CEACAM6, APOC1 and YF13H12 [5].

Psychiatry related information on APOC1

• Since a deletion/insertion polymorphism in the promoter region of the apolipoprotein C-I (APOC1) gene has been reported to be associated with late-onset Alzheimer's disease (LOAD), we examined the hypothesis in a Korean population with 120 LOAD cases and 132 age-matched controls [6].
• Previous research has shown that polymorphisms of the apolipoproteins E ( APOE) and APOC1 represent genetic risk factors for dementia and for cognitive impairment in the elderly [7].

High impact information on APOC1

• At 2 mo of age, serum levels of cholesterol, triglycerides (TG), and FFA were strongly elevated in APOC1 transgenic mice compared with wild-type mice [8].
• Transgenic mice were generated with different levels of human apolipoprotein C1 (APOC1) expression in liver and skin [8].
• In line with these results, epidermal lipid analysis showed that the relative amounts of the sebum components TG and wax diesters in the epidermis of high expressor APOC1 transgenic mice were reduced by 60 and 45%, respectively [8].
• In addition to atrophic sebaceous glands, the meibomian glands were also found to be severely atrophic in APOC1 transgenic mice [8].
• Since these skin abnormalities appeared in two independent founder lines, a mutation related to the specific insertion site of the human APOC1 gene as the cause for the phenotype can be excluded [8].

Chemical compound and disease context of APOC1

• Primary hyperlipidaemia alone in APOC1 mice does not lead to insulin resistance for glucose metabolism and high blood pressure [9].
• Apolipoprotein CI stimulates the response to lipopolysaccharide and reduces mortality in gram-negative sepsis [10].

Biological context of APOC1

• In addition, APOC1 seems to be an interesting marker because, though in strict linkage disequilibrium with APOE, it seems to play an independent role in AD risk [11].
• However, we observed a significant difference in the genotype and allele frequencies of APOE and APOC1: patients had higher e*4 and C1*2 allele frequencies [11].
• Overlapping cosmid clones allowed the construction of a detailed restriction map of the gene cluster, showing the APOC2 gene to be located 15 kb downstream of the APOC1 pseudogene [2].
• In the present paper we show by molecular cloning and sequencing that the polymorphic HpaI site is located 317 bp upstream of the transcription initiation site of the APOC1 gene [2].
• These data indicate that the hyperlipidemia in APOC1 transgenic mice results primarily from impaired hepatic VLDL particle clearance, rather than a defect in the hydrolysis of VLDL-triglyceride [12].

Anatomical context of APOC1

• Further, we found an association between the A allele of the apolipoprotein C1 (APOC1) polymorphism and poorer memory and frontal lobe function [13].
• High expressor APOC1 transgenic mice also exhibited diminished abdominal adipose tissue stores (a 60% decrease compared with wild-type mice) and a complete deficiency of subcutaneous fat [8].
• Although less pronounced, APOC1 overexpression also reduced body weight on a wild-type background, solely due to a reduction in adipose tissue [14].
• Multiple regression analyses showed that the APOC1 polymorphism was the only variable which predicted NAA/Cr values in basal ganglia [15].
• Effect of atorvastatin on ApoE and ApoC-I synthesis and secretion by THP-1 macrophages [16].

Associations of APOC1 with chemical compounds

• Hyperinsulinemic clamp analysis revealed severe whole-body and hepatic insulin resistance in obob/APOC1(+/-) mice and, in addition, increased hepatic uptake of FFA and hepatic TG content [3].
• We conclude that overexpression of APOC1 prevents rosiglitazone-induced peripheral FA uptake leading to severe hepatic steatosis [3].
• Using hyperinsulinemic-euglycemic clamp tests, we previously found that in APOC1 transgenic mice, the whole-body insulin-mediated glucose uptake is increased concomitant with a decreased fatty acid uptake [14].
• These latter results are confirmed in the present study, showing that APOC1 transgenic mice exhibit a 50% reduction in the uptake of the fatty acid analog 15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid in white adipose tissue stores [14].
• Conformation of two peptides corresponding to human apolipoprotein C-I residues 7-24 and 35-53 in the presence of sodium dodecyl sulfate by CD and NMR spectroscopy [17].

Regulatory relationships of APOC1

• Apolipoprotein CI overexpression is not a relevant strategy to block cholesteryl ester transfer protein (CETP) activity in CETP transgenic mice [18].
• ApoC-I activated LCAT to the same extent with both saturated and unsaturated phosphatidylcholine substrates [19].

Other interactions of APOC1

• When taken together with previous studies, our results suggest the following physical gene map: pter-LDLR-C3-p13.2-PEPD-centromere-(APOE, APOC1, APOC2, GPI)-qter [1].
• We conclude that, apart from the ApoE allele 4, other genetically regulated factors like ApoCI and the LDL receptor modulate the individual risk for Alzheimer's disease [20].
• APOE and APOC1 promoter polymorphisms and the risk of Alzheimer disease in African American and Caribbean Hispanic individuals [21].
• Two of the markers, APOC1 and APOC2, are tightly linked to DM [22].
• The high values of APOE*E4 and LPA PNR*7 together with the intermediate linkage disequilibrium values between APOE and APOC1 alleles in comparison with Europeans and Africans suggest a certain degree of Sub-Saharan influence in the current Moroccan population [23].

Analytical, diagnostic and therapeutic context of APOC1

• METHODS: This method included newly designed primers and only one round of PCR amplification which yields one short and specific APOC1 fragment followed by HpaI digestion [24].
• ApoC-I and apoE were measured by ELISA in total plasma and in very low-density lipoproteins (VLDL) separated by ultracentrifugation (d<1.006 g/ml), and then by difference for the non-VLDL fraction (d>1.006 g/ml), in a subset of families selected for their diverse apoE genotypes [25].
• Labeling of apolipoprotein C-I by the Bolton and Hunter reagent allowed a study of the kinetics of this peptide in normolipidemic human volunteers [26].
• In order to gain new insights into the function of the individual apoCs in lipoprotein metabolism, several laboratories have created mouse models lacking or overexpressing the respective APOC genes through the technologies of gene targeting and transgenesis [27].
• Crystallization and preliminary X-ray analysis of human plasma apolipoprotein C-I [28].

References