title: DNA Methylation and High-Density Lipoprotein Functionality-Brief Report: The REGICOR Study (Registre Gironi del Cor).
abstract: OBJECTIVE
  The function of high-density lipoproteins (HDLs) may better reflect their atheroprotective role, compared with HDL-cholesterol levels. The association between DNA methylation and HDL function has not yet been established.
  
  
  RESULTS
  We designed an epigenome-wide association study including 645 individuals from the REGICOR study (Registre Gironi del Cor). We determined DNA methylation from peripheral blood cells using the HumanMethylation450 array. We analyzed HDL functionality by determining HDL cholesterol efflux capacity and HDL inflammatory index. We discovered 3 methylation sites located inHOXA3,PEX5, andPER3related to cholesterol efflux capacity and 1 located inGABRR1related to HDL inflammatory index. Using a candidate gene approach, we also found 2 methylation sites located inCMIPrelated to cholesterol efflux capacity.
  
  
  CONCLUSIONS
  We identified 6 potential loci associated with HDL functionality inHOXA3,PEX5,PER3, CMIP, andGABRR1. Additional studies are warranted to validate these findings in other populations.
authors.affiliation: From the IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (S.S.-B., A.H., I.S., C.L.-G., D.M., M.F., J.M., R.E.); Universitat Pompeu Fabra (UPF), Barcelona, Spain (S.S.-B.); and CIBER (Centro de Investigación Biomédica en Red) de Enfermedades Cardiovasculares (CIBERCV) (S.S.-B., J.M., R.E.), CIBER de Fisiopatología de la Nutrición y la Obesidad (CIBEROBN) (A.H., D.M., M.F.) and CIBER de Epidemiología y Salud Pública (CIBERESP) (I.S.), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Sayols-Baixeras
authors.affiliation: From the IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (S.S.-B., A.H., I.S., C.L.-G., D.M., M.F., J.M., R.E.); Universitat Pompeu Fabra (UPF), Barcelona, Spain (S.S.-B.); and CIBER (Centro de Investigación Biomédica en Red) de Enfermedades Cardiovasculares (CIBERCV) (S.S.-B., J.M., R.E.), CIBER de Fisiopatología de la Nutrición y la Obesidad (CIBEROBN) (A.H., D.M., M.F.) and CIBER de Epidemiología y Salud Pública (CIBERESP) (I.S.), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Hernáez
authors.affiliation: From the IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (S.S.-B., A.H., I.S., C.L.-G., D.M., M.F., J.M., R.E.); Universitat Pompeu Fabra (UPF), Barcelona, Spain (S.S.-B.); and CIBER (Centro de Investigación Biomédica en Red) de Enfermedades Cardiovasculares (CIBERCV) (S.S.-B., J.M., R.E.), CIBER de Fisiopatología de la Nutrición y la Obesidad (CIBEROBN) (A.H., D.M., M.F.) and CIBER de Epidemiología y Salud Pública (CIBERESP) (I.S.), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Issac
authors.initials: I
authors.lastname: Subirana
authors.affiliation: From the IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (S.S.-B., A.H., I.S., C.L.-G., D.M., M.F., J.M., R.E.); Universitat Pompeu Fabra (UPF), Barcelona, Spain (S.S.-B.); and CIBER (Centro de Investigación Biomédica en Red) de Enfermedades Cardiovasculares (CIBERCV) (S.S.-B., J.M., R.E.), CIBER de Fisiopatología de la Nutrición y la Obesidad (CIBEROBN) (A.H., D.M., M.F.) and CIBER de Epidemiología y Salud Pública (CIBERESP) (I.S.), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Carla
authors.initials: C
authors.lastname: Lluis-Ganella
authors.affiliation: From the IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (S.S.-B., A.H., I.S., C.L.-G., D.M., M.F., J.M., R.E.); Universitat Pompeu Fabra (UPF), Barcelona, Spain (S.S.-B.); and CIBER (Centro de Investigación Biomédica en Red) de Enfermedades Cardiovasculares (CIBERCV) (S.S.-B., J.M., R.E.), CIBER de Fisiopatología de la Nutrición y la Obesidad (CIBEROBN) (A.H., D.M., M.F.) and CIBER de Epidemiología y Salud Pública (CIBERESP) (I.S.), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Muñoz
authors.affiliation: From the IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (S.S.-B., A.H., I.S., C.L.-G., D.M., M.F., J.M., R.E.); Universitat Pompeu Fabra (UPF), Barcelona, Spain (S.S.-B.); and CIBER (Centro de Investigación Biomédica en Red) de Enfermedades Cardiovasculares (CIBERCV) (S.S.-B., J.M., R.E.), CIBER de Fisiopatología de la Nutrición y la Obesidad (CIBEROBN) (A.H., D.M., M.F.) and CIBER de Epidemiología y Salud Pública (CIBERESP) (I.S.), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Fitó
authors.affiliation: From the IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (S.S.-B., A.H., I.S., C.L.-G., D.M., M.F., J.M., R.E.); Universitat Pompeu Fabra (UPF), Barcelona, Spain (S.S.-B.); and CIBER (Centro de Investigación Biomédica en Red) de Enfermedades Cardiovasculares (CIBERCV) (S.S.-B., J.M., R.E.), CIBER de Fisiopatología de la Nutrición y la Obesidad (CIBEROBN) (A.H., D.M., M.F.) and CIBER de Epidemiología y Salud Pública (CIBERESP) (I.S.), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Marrugat
authors.affiliation: From the IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (S.S.-B., A.H., I.S., C.L.-G., D.M., M.F., J.M., R.E.); Universitat Pompeu Fabra (UPF), Barcelona, Spain (S.S.-B.); and CIBER (Centro de Investigación Biomédica en Red) de Enfermedades Cardiovasculares (CIBERCV) (S.S.-B., J.M., R.E.), CIBER de Fisiopatología de la Nutrición y la Obesidad (CIBEROBN) (A.H., D.M., M.F.) and CIBER de Epidemiología y Salud Pública (CIBERESP) (I.S.), Instituto de Salud Carlos III, Madrid, Spain. relosua@imim.es.
authors.forename: Roberto
authors.initials: R
authors.lastname: Elosua
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D045744:Cell Line, Tumor; D008076:Cholesterol, HDL / Q000097:blood*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D056950:Period Circadian Proteins / Q000235:genetics; D000074435:Peroxisome-Targeting Signal 1 Receptor; D010641:Phenotype; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics; D013030:Spain
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; C540426:CMIP protein, human; D008076:Cholesterol, HDL; C547868:GABRR1 protein, human; C489832:HOXA3 protein, human; D018398:Homeodomain Proteins; C512644:PER3 protein, human; C000614264:PEX5 protein, human; D056950:Period Circadian Proteins; D000074435:Peroxisome-Targeting Signal 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011963:Receptors, GABA-A
keywords: DNA methylation; atherosclerosis; blood cells; lipoproteins; risk factors