{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T08:51:00Z","timestamp":1769763060806,"version":"3.49.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>\n              Fatty acid\u2013binding protein 4 (FABP4 or\n              <jats:italic>aP2<\/jats:italic>\n              in mice) has been identified as a key regulator of core aspects of cardiometabolic disorders, including lipotoxic endoplasmic reticulum stress in macrophages. A functional promoter polymorphism (\n              <jats:italic>rs77878271<\/jats:italic>\n              ) of human\n              <jats:italic>FABP4<\/jats:italic>\n              gene has been described resulting in reduced FABP4 transcription.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              We investigated the effects of this low-expression variant of\n              <jats:italic>FABP4<\/jats:italic>\n              on cardiovascular morbidity and carotid atherosclerosis on a population level (n=7491) and in patient cohorts representing endarterectomized patients with advanced carotid atherosclerosis (n=92) and myocardial infarction (n=3432). We found that the low-expression variant was associated with decreased total cholesterol levels (\n              <jats:italic>P<\/jats:italic>\n              =0.006) with the largest reduction in variant allele homozygotes. Obese variant allele carriers also showed reduced carotid intima-media thickness (\n              <jats:italic>P<\/jats:italic>\n              =0.010) and lower prevalence of carotid plaques (\n              <jats:italic>P<\/jats:italic>\n              =0.060). Consistently, the variant allele homozygotes showed 8-fold lower odds for myocardial infarction (\n              <jats:italic>P<\/jats:italic>\n              =0.019; odds ratio, 0.12; 95% confidence interval, 0.003\u20130.801). Within the carotid plaques, the variant allele was associated with a 3.8-fold reduction in FABP4 transcription (\n              <jats:italic>P<\/jats:italic>\n              =0.049) and 2.7-fold reduction in apoptosis (activated caspase 3;\n              <jats:italic>P<\/jats:italic>\n              =0.043). Furthermore, the variant allele was enriched to patients with asymptomatic carotid stenosis (\n              <jats:italic>P<\/jats:italic>\n              =0.038). High FABP4 expression in the carotid plaques was associated with lipid accumulation, intraplaque hemorrhages, plaque ulcerations, and phosphoactivated endoplasmic reticulum stress markers.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              Our results reveal\n              <jats:italic>FABP4 rs77878271<\/jats:italic>\n              as a novel variant affecting serum total cholesterol levels and cardiovascular risk. A therapeutic regimen reducing FABP4 expression within the atherosclerotic plaque may promote lesion stability through modulation of endoplasmic reticulum stress signaling, and attenuation of apoptosis, lipid burden, and inflammation.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgenetics.113.000499","type":"journal-article","created":{"date-parts":[[2014,8,14]],"date-time":"2014-08-14T04:35:20Z","timestamp":1407990920000},"page":"588-598","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Low-Expression Variant of Fatty Acid\u2013Binding Protein 4 Favors Reduced Manifestations of Atherosclerotic Disease and Increased Plaque Stability"],"prefix":"10.1161","volume":"7","author":[{"given":"Jani","family":"Saksi","sequence":"first","affiliation":[{"name":"From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Ij\u00e4s","sequence":"additional","affiliation":[{"name":"From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikko I.","family":"M\u00e4yr\u00e4np\u00e4\u00e4","sequence":"additional","affiliation":[{"name":"From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krista","family":"Nuotio","sequence":"additional","affiliation":[{"name":"From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pia M.","family":"Isoviita","sequence":"additional","affiliation":[{"name":"From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jarno","family":"Tuimala","sequence":"additional","affiliation":[{"name":"From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erno","family":"Lehtonen-Smeds","sequence":"additional","affiliation":[{"name":"From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markku","family":"Kaste","sequence":"additional","affiliation":[{"name":"From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antti","family":"Jula","sequence":"additional","affiliation":[{"name":"From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); 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