HGNC Approved Gene Symbol: APOC1
Cytogenetic location: 19q13.32 Genomic coordinates (GRCh38): 19:44,914,325-44,919,346 (from NCBI)
Tata et al. (1985) synthesized a mixed oligonucleotide 17 bases long and used it to isolate cDNA clones for apoC-I from an adult liver cDNA library.
Tata et al. (1985) used a probe and Southern blot techniques to identify the human APOC1 gene in the DNA of various human-rodent cell hybrids. Their results assigned the gene to chromosome 19.
By the study of somatic cell hybrids containing rearranged chromosome 19, Scott et al. (1985) concluded that the chromosome 19 cluster of apolipoprotein genes probably lies in the 19p13-19cen region. (HGM8 placed the cluster in the 19cen-19q13 region.) Davison et al. (1986) showed that there are 2 APOC1 sequences on chromosome 19 and that 1 of them is 4 kb 3-prime to apolipoprotein E (APOE; 107741) and oriented in the same way as APOE. One APOC1 gene appeared to be a pseudogene because no mRNA product could be detected in any tissue (Lauer et al., 1988). There are 2 APOC1 mRNA transcripts, but these may be the consequence of differential processing of a single primary transcript.
Lusis et al. (1986) used a reciprocal whole arm translocation between the long arm of chromosome 19 and the short arm of chromosome 1 to determine that the APOC1, APOC2, APOE and GPI loci are on the long arm and the LDLR, C3 and PEPD loci on the short arm. They isolated a single lambda phage carrying APOC1 and part of APOE. These genes are 6 kb apart and arranged tandemly. APOC2 and APOE were previously shown to be tightly linked. Studying a cDNA APOC1 clone and a genomic APOE clone, Myklebost and Rogne (1986) concluded that the loci are 4.3 kb apart. By comparison, on chromosome 11, APOA1 (107680) is 2.6 kb from APOC3 (107720). Using separate probes for each locus, Bailey and Miller (1987) mapped APOC2 and APOE to 19q13.1 at the border of q12 by in situ hybridization.
Smit et al. (1988) presented a map of the apolipoprotein E-C1-C2 gene cluster on chromosome 19: 5-prime--APOE--4.3 kb--APOC1--6 kb--APOC1 pseudogene--about 22 kb--APOC2--3-prime. Thus, the cluster spans approximately 48 kb. This gene order and the size of the cluster were confirmed by Myklebost and Rogne (1988) by pulsed-field gel electrophoresis mapping methods. A HpaI RFLP in the APOE-C1-C2 gene cluster on chromosome 19 is strongly associated with familial dysbetalipoproteinemia. Smit et al. (1988) showed that this RFLP site is between APOE and APOC1 and specifically that it is located 317 bp upstream of the transcription initiation site of the APOC1 gene. They constructed a detailed restriction map of the gene cluster, showing that the APOC2 gene is located 15 kb downstream of the APOC1 pseudogene. Although Trask et al. (1993) did not map the APOC1 gene directly, the mapping of the APOE and APOC2 genes to 19q13.2 by fluorescence in situ hybridization established that the APOC1 gene is also in this band.
Age-associated memory impairment (AAMI) is a designation used to define the nondemented elderly with subjective and objective memory impairment presenting no medical or other psychopathologic conditions that could explain the memory problems (Crook et al., 1986). Bartres-Faz et al. (2001) noted that it was controversial whether AAMI described a subgroup of normally aging subjects or, on the other hand, whether these individuals presented particular characteristics distinguishable from controls or an intermediate stage between normal aging and dementia. Because an association between an APOE polymorphism (APOE*E4; 107741.0016) and late-onset Alzheimer disease (104310) had been convincingly confirmed in several reports, they studied the distribution of genetic polymorphisms in the APOE and APOC1 genes in a sample of 100 subjects fulfilling the National Institute of Mental Health criteria for age-associated memory impairment and in 124 controls. They found significant associations for both APOE and APOC1 and their combinations with the AAMI condition.
To determine the relationship between APOC1 and CETP (118470), Gautier et al. (2002) crossed transgenic mice expressing human CETP with Apoc1 null mice. The high density lipoproteins (HDLs) of these crosses contained 50% less cholesteryl esters and showed a decreased cholesteryl ester-to-triglyceride ratio. The mean apparent diameter of LDLs from these mice was also significantly reduced. In vitro, purified Apoc1 inhibited cholesteryl ester exchange when added to either total plasma or to reconstituted HDL-free mixtures. Gautier et al. (2002) concluded that APOC1 is a specific inhibitor of CETP.
Jong et al. (1999) found that adenovirus-delivery of LDLR (606945) to transgenic mice overexpressing Apoc1 resulted in decreased plasma lipid levels. Infection with VLDLR (192977) had no effect. These results, coupled with in vitro binding studies, suggested that APOC1 inhibits the clearance of lipoprotein particles via VLDLR, but APOC1-enriched lipoproteins can still bind to LDLR.
Bailey, R., Miller, D. A. Mapping the human apolipoprotein genes CII and E to band 19q13.1 by in situ hybridization. (Abstract) Am. J. Hum. Genet. 41: A156 only, 1987.
Bartres-Faz, D., Clemente, I. C., Junque, C., Valveny, N., Lopez-Alomar, A., Sanchez-Aldeguer, J., Lopez-Guillen, A., Moral, P. APOE and APOC1 genetic polymorphisms in age-associated memory impairment. Neurogenetics 3: 215-219, 2001. [PubMed: 11714102] [Full Text: https://doi.org/10.1007/s100480100122]
Crook, T. H., Bartus, R. T., Ferris, S. H., Whitehouse, P., Cohen, G. D., Gershon, S. Age-associated memory impairment: proposed diagnostic criteria and measures of clinical change. Report of a National Institute of Mental Health work group. Dev. Neuropsychol. 2: 261-276, 1986.
Davison, P. J., Norton, P., Wallis, S. C., Gill, L., Cook, M., Williamson, R., Humphries, S. E. There are two gene sequences for human apolipoprotein CI (APO CI) on chromosome 19, one of which is 4 kb from the gene for APO E. Biochem. Biophys. Res. Commun. 136: 876-884, 1986. [PubMed: 3013172] [Full Text: https://doi.org/10.1016/0006-291x(86)90414-6]
Gautier, T., Masson, D., Jong, M. C., Duverneuil, L., Le Guern, N., Deckert, V., Pais de Barros, J.-P., Dumont, L., Bataille, A., Zak, Z., Jiang, X.-C., Tall, A. R., Havekes, L. M., Lagrost, L. Apolipoprotein CI deficiency markedly augments plasma lipoprotein changes mediated by human cholesteryl ester transfer protein (CETP) in CETP transgenic/ApoCI-knocked out mice. J. Biol. Chem. 277: 31354-31363, 2002. [PubMed: 12070157] [Full Text: https://doi.org/10.1074/jbc.M203151200]
Jong, M. C., Van Dijk, K. W., Dahlmans, V. E. H., Van Der Boom, H., Kobayashi, K., Oka, K., Siest, G., Chan, L., Hofker, M. H., Havekes, L. M. Reversal of hyperlipidaemia in apolipoprotein C1 transgenic mice by adenovirus-mediated gene delivery of the low-density-lipoprotein receptor, but not by the very low-density-lipoprotein receptor. Biochem. J. 338: 281-287, 1999. [PubMed: 10024503]
Lauer, S. J., Walker, D., Elshourbagy, N. A., Reardon, C. A., Levy-Wilson, B., Taylor, J. M. Two copies of the human apolipoprotein C-I gene are linked closely to the apolipoprotein E gene. J. Biol. Chem. 263: 7277-7286, 1988. [PubMed: 2835369]
Lusis, A. J., Heinzmann, C., Sparkes, R. S., Scott, J., Knott, T. J., Geller, R., Sparkes, M. C., Mohandas, T. Regional mapping of human chromosome 19: organization of genes for plasma lipid transport (APOC1, -C2, and -E and LDLR) and the genes C3, PEPD, and GPI. Proc. Nat. Acad. Sci. 83: 3929-3933, 1986. [PubMed: 3459164] [Full Text: https://doi.org/10.1073/pnas.83.11.3929]
Myklebost, O., Rogne, S. The gene for human apolipoprotein CI is located 4.3 kilobases away from the apolipoprotein E gene on chromosome 19. Hum. Genet. 73: 286-289, 1986. [PubMed: 3017837] [Full Text: https://doi.org/10.1007/BF00279087]
Myklebost, O., Rogne, S. A physical map of the apolipoprotein gene cluster on human chromosome 19. Hum. Genet. 78: 244-247, 1988. [PubMed: 2894348] [Full Text: https://doi.org/10.1007/BF00291670]
Scott, J., Knott, T. J., Shaw, D. J., Brook, J. D. Localization of genes encoding apolipoproteins CI, CII, and E to the p13-cen region of human chromosome 19. Hum. Genet. 71: 144-146, 1985. [PubMed: 2995235] [Full Text: https://doi.org/10.1007/BF00283370]
Smit, M., van der Kooij-Meijs, E., Frants, R. R., Havekes, L., Klasen, E. C. Apolipoprotein gene cluster on chromosome 19: definite localization of the APOC2 gene and the polymorphic HpaI site associated with type III hyperlipoproteinemia. Hum. Genet. 78: 90-93, 1988. [PubMed: 2892779] [Full Text: https://doi.org/10.1007/BF00291243]
Smit, M., van der Kooij-Meijs, E., Woudt, L. P., Havekes, L. M., Frants, R. R. Exact localization of the familial dysbetalipoproteinemia associated HpaI restriction site in the promoter region of the APOC1 gene. Biochem. Biophys. Res. Commun. 152: 1282-1288, 1988. [PubMed: 2897845] [Full Text: https://doi.org/10.1016/s0006-291x(88)80424-8]
Tata, F., Henry, I., Markham, A. F., Wallis, S. C., Weil, D., Grzeschik, K. H., Junien, C., Williamson, R., Humphries, S. E. Isolation and characterisation of a cDNA clone for human apolipoprotein CI and assignment of the gene to chromosome 19. Hum. Genet. 69: 345-349, 1985. [PubMed: 2985493] [Full Text: https://doi.org/10.1007/BF00291654]
Trask, B., Fertitta, A., Christensen, M., Youngblom, J., Bergmann, A., Copeland, A., de Jong, P., Mohrenweiser, H., Olsen, A., Carrano, A., Tynan, K. Fluorescence in situ hybridization mapping of human chromosome 19: cytogenetic band location of 540 cosmids and 70 genes or DNA markers. Genomics 15: 133-145, 1993. [PubMed: 8432525] [Full Text: https://doi.org/10.1006/geno.1993.1021]