{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:22:05Z","timestamp":1791242525943,"version":"4.1.0"},"reference-count":107,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,1,17]],"date-time":"2008-01-17T00:00:00Z","timestamp":1200528000000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although in developing countries an apolipoprotein E4 (apoE4) genotype may offer an evolutionary advantage, as it has been shown to offer protection against certain infectious disease, in Westernised societies it is associated with increased morbidity and mortality, and represents a significant risk factor for cardiovascular disease, late\u2010onset Alzheimer's disease and other chronic disorders. ApoE is an important modulator of many stages of lipoprotein metabolism and traditionally the increased risk was attributed to higher lipid levels in E4 carriers. However, more recent evidence demonstrates the multifunctional nature of the apoE protein and the fact that the impact of genotype on disease risk may be in large part due to an impact on oxidative status or the immunomodulatory\/anti\u2010inflammatory properties of apoE. An increasing number of studies in cell lines, targeted replacement rodents and human volunteers indicate higher oxidative stress and a more pro\u2010inflammatory state associated with the \u03b54 allele. The impact of genotype on the antioxidant and immunomodulatory\/anti\u2010inflammatory properties of apoE is the focus of the current review. Furthermore, current information on the impact of environment (diet, exercise, smoking status, alcohol) on apoE genotype\u2010phenotype associations are discussed with a view to identifying particular lifestyle strategies that could be adapted to counteract the \u2018at\u2010risk\u2019 E4 genotype.<\/jats:p>","DOI":"10.1002\/mnfr.200700322","type":"journal-article","created":{"date-parts":[[2008,1,17]],"date-time":"2008-01-17T23:07:19Z","timestamp":1200611239000},"page":"131-145","source":"Crossref","is-referenced-by-count":267,"title":["Impact of apoE genotype on oxidative stress, inflammation and disease risk"],"prefix":"10.1002","volume":"52","author":[{"given":"Laia","family":"Jofre\u2010Monseny","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Marie","family":"Minihane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Rimbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,1,17]]},"reference":[{"key":"e_1_2_1_2_2","unstructured":"WHO Cardiovascular diseases World Health Organization. 2007 Fact sheet 317."},{"key":"e_1_2_1_3_2","first-page":"39","article-title":"Alzheimer's disease: Of emerging Importance","volume":"6","author":"Chicot J. V.","year":"2002","journal-title":"WHO Regional Health Forum"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-141-2-200407200-00013"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665107005435"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.12.7545"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(85)90704-0"},{"key":"e_1_2_1_8_2","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1016\/S0021-9258(18)89575-8","article-title":"Quantitation of apolipoprotein E mRNA in the liver and peripheral tissues of nonhuman primates.","volume":"260","author":"Newman T. C.","year":"1985","journal-title":"J. Biol. Chem."},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199604100-00010"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb06365.x"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(94)90156-2"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.1.89"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118271"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117687"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104812200"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi026202k"},{"key":"e_1_2_1_17_2","doi-asserted-by":"crossref","first-page":"4171","DOI":"10.1016\/S0021-9258(18)34702-1","article-title":"Human apolipoprotein E. The complete amino acid sequence.","volume":"257","author":"Rall S. C.","year":"1982","journal-title":"J. Biol. Chem."},{"key":"e_1_2_1_18_2","doi-asserted-by":"crossref","first-page":"9077","DOI":"10.1016\/S0021-9258(19)52510-8","article-title":"Human E apoprotein heterogeneity. Cysteine\u2010arginine interchanges in the amino acid sequence of the apo\u2010E isoforms.","volume":"256","author":"Weisgraber K. H.","year":"1981","journal-title":"J. Biol. Chem."},{"key":"e_1_2_1_19_2","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1016\/S0021-9258(18)34954-8","article-title":"Abnormal lipoprotein receptor\u2010binding activity of the human E apoprotein due to cysteine\u2010arginine interchange at a single site.","volume":"257","author":"Weisgraber K. H.","year":"1982","journal-title":"J. Biol. Chem."},{"key":"e_1_2_1_20_2","doi-asserted-by":"crossref","first-page":"7261","DOI":"10.1016\/S0021-9258(17)39866-6","article-title":"Normalization of receptor binding of apolipoprotein E2. Evidence for modulation of the binding site conformation.","volume":"259","author":"Innerarity T. L.","year":"1984","journal-title":"J. Biol. Chem."},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2006.06.008"},{"key":"e_1_2_1_22_2","doi-asserted-by":"crossref","first-page":"22358","DOI":"10.1016\/S0021-9258(17)31797-0","article-title":"Human apolipoprotein E. Role of arginine 61 in mediating the lipoprotein preferences of the E3 and E4 isoforms.","volume":"269","author":"Dong L. M.","year":"1994","journal-title":"J. Biol. Chem."},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1177\/147323000703500114"},{"key":"e_1_2_1_24_2","first-page":"2280","article-title":"The Apolipoprotein E and \u03b2\u2010fibrinogen G\/A\u2010455 gene polymorphisms are associated with ischemic stroke involving large\u2010vessel disease.","volume":"17","author":"Kesseler C.","year":"1997","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyh214"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1934"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)04318-3"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.52.2.244"},{"key":"e_1_2_1_29_2","first-page":"451","article-title":"Apolipoprotein E4 genotype increases the risk of postoperative cognitive dysfunction in patients undergoing coronary artery bypass graft surgery.","volume":"47","author":"Lelis R. G.","year":"2006","journal-title":"J. Cardiovasc. Surg. (Torino)"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-4975(95)00076-W"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2006.01360.x"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/2677"},{"key":"e_1_2_1_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2005.06950.x"},{"key":"e_1_2_1_34_2","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.1182\/blood.V92.9.3455","article-title":"Apolipoprotein E epsilon4 allele as a genetic risk factor for left ventricular failure in homozygous beta\u2010thalassemia.","volume":"92","author":"Economou\u2010Petersen E.","year":"1998","journal-title":"Blood"},{"key":"e_1_2_1_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwj279"},{"key":"e_1_2_1_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2006.09.049"},{"key":"e_1_2_1_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2006.09.036"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000148719.82468.CA"},{"key":"e_1_2_1_39_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.34745"},{"key":"e_1_2_1_40_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.1883"},{"key":"e_1_2_1_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/2685"},{"key":"e_1_2_1_42_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003324200"},{"key":"e_1_2_1_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10209"},{"key":"e_1_2_1_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0996-55"},{"key":"e_1_2_1_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(99)00102-1"},{"key":"e_1_2_1_46_2","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1999.0273"},{"key":"e_1_2_1_47_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.12.2319"},{"key":"e_1_2_1_48_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0404.2000.102006346.x"},{"key":"e_1_2_1_49_2","first-page":"179","article-title":"Influence of apolipoprotein E genotype on blood redox status of Alzheimer's disease patients.","volume":"4","author":"Fernandes M. A.","year":"1999","journal-title":"Int. J. Mol. Med."},{"key":"e_1_2_1_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)03228-0"},{"key":"e_1_2_1_51_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02532.x"},{"key":"e_1_2_1_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)05330-2"},{"key":"e_1_2_1_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(00)00570-0"},{"key":"e_1_2_1_54_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8817.2005.00205.x"},{"key":"e_1_2_1_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2006.01.008"},{"key":"e_1_2_1_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11745-006-1390-4"},{"key":"e_1_2_1_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5122(01)00171-2"},{"key":"e_1_2_1_58_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114507669219"},{"key":"e_1_2_1_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10697"},{"key":"e_1_2_1_60_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0472696"},{"key":"e_1_2_1_61_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0741426.x"},{"key":"e_1_2_1_62_2","doi-asserted-by":"crossref","first-page":"3716","DOI":"10.4049\/jimmunol.136.10.3716","article-title":"Apolipoprotein E is a biologically active constituent of the normal immunoregulatory lipoprotein, LDL\u2010In.","volume":"136","author":"Pepe M. G.","year":"1986","journal-title":"J. Immunol."},{"key":"e_1_2_1_63_2","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1994.1302"},{"key":"e_1_2_1_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(95)80004-3"},{"key":"e_1_2_1_65_2","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1016\/S0022-2275(20)32160-X","article-title":"Apolipoprotein E\u2010deficient mice have impaired innate immune responses to Listeria monocytogenes in vivo.","volume":"39","author":"Roselaar S. E.","year":"1998","journal-title":"J. Lipid Res."},{"key":"e_1_2_1_66_2","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/S0022-2275(20)32147-7","article-title":"Apolipoprotein E knock\u2010out mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection.","volume":"40","author":"de Bont N.","year":"1999","journal-title":"J. Lipid Res."},{"key":"e_1_2_1_67_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009915200"},{"key":"e_1_2_1_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(97)00021-0"},{"key":"e_1_2_1_69_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1998.tb00166.x"},{"key":"e_1_2_1_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(00)00459-8"},{"key":"e_1_2_1_71_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306923200"},{"key":"e_1_2_1_72_2","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:23:3:205"},{"key":"e_1_2_1_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.05.002"},{"key":"e_1_2_1_74_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-5423fje"},{"key":"e_1_2_1_75_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-3-10"},{"key":"e_1_2_1_76_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb04070.x"},{"key":"e_1_2_1_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00016-7"},{"key":"e_1_2_1_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.03.150"},{"key":"e_1_2_1_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2007.01.019"},{"key":"e_1_2_1_80_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.70.4.677"},{"key":"e_1_2_1_81_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M500114-JLR200"},{"key":"e_1_2_1_82_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.10.5901"},{"key":"e_1_2_1_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1010-7940(01)00842-9"},{"key":"e_1_2_1_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.08.032"},{"key":"e_1_2_1_85_2","doi-asserted-by":"publisher","DOI":"10.1155\/MI\/2006\/12587"},{"key":"e_1_2_1_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ehj.2004.08.024"},{"key":"e_1_2_1_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(01)00480-4"},{"key":"e_1_2_1_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2004.07.012"},{"key":"e_1_2_1_89_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000052939.59093.45"},{"key":"e_1_2_1_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.03.004"},{"key":"e_1_2_1_91_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000014325.54063.1A"},{"key":"e_1_2_1_92_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/73.4.736"},{"key":"e_1_2_1_93_2","doi-asserted-by":"publisher","DOI":"10.1053\/meta.2001.24867"},{"key":"e_1_2_1_94_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/80.6.1639"},{"key":"e_1_2_1_95_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38181.418958.BE"},{"key":"e_1_2_1_96_2","doi-asserted-by":"publisher","DOI":"10.1249\/01.mss.0000239399.85955.5e"},{"key":"e_1_2_1_97_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00813-X"},{"key":"e_1_2_1_98_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.10.029"},{"key":"e_1_2_1_99_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1331.006"},{"key":"e_1_2_1_100_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.2002.00983.x"},{"key":"e_1_2_1_101_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0047-6374(02)00008-8"},{"key":"e_1_2_1_102_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_2_1_103_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)91705-Q"},{"key":"e_1_2_1_104_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.16.10.1250"},{"key":"e_1_2_1_105_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(99)00232-4"},{"key":"e_1_2_1_106_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2004.02145.x"},{"key":"e_1_2_1_107_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.18.9.1424"},{"key":"e_1_2_1_108_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2003.01665.x"}],"container-title":["Molecular Nutrition &amp; Food Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmnfr.200700322","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mnfr.200700322","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T11:21:29Z","timestamp":1700047289000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mnfr.200700322"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1]]},"references-count":107,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,1]]}},"alternative-id":["10.1002\/mnfr.200700322"],"URL":"https:\/\/doi.org\/10.1002\/mnfr.200700322","archive":["Portico"],"relation":{},"ISSN":["1613-4125","1613-4133"],"issn-type":[{"value":"1613-4125","type":"print"},{"value":"1613-4133","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1]]}}}