Functional Analysis of a Carotid Intima-Media Thickness Locus Implicates BCAR1 and Suggests a Causal Variant.
BACKGROUND
Carotid intima-media thickness (IMT) is a marker of subclinical atherosclerosis that can predict cardiovascular disease events over traditional risk factors. This study examined the BCAR1-CFDP1-TMEM170A locus on chromosome 16, associated with carotid IMT and coronary artery disease in the IMT and IMT-Progression as Predictors of Vascular Events (IMPROVE) cohort, to identify the functional variant.


RESULTS
In analysis of the locus lead single nucleotide polymorphism (SNP; rs4888378, intronic in CFDP1) in Progressione della Lesione Intimale Carotidea (PLIC), the protective AA genotype was associated with slower IMT progression in women (P=0.04) but not in men. Meta-analysis of 5 cohort studies also supported a protective effect of the A allele on common carotid IMT in women only (women: β=-0.0047, P=1.63 × 10(-4); men: β=-0.0029, P=0.0678). Two hundred fourteen noncoding variants in strong linkage disequilibrium (r(2) ≥ 0.8) with rs4888378 were identified from 1000 Genome Project. ENCODE regulatory chromatin marks were used to create a shortlist of 6 possible regulatory variants. Electrophoretic mobility shift assays on the shortlist detected allele-specific protein binding to the lead SNP rs4888378; multiplexed competitor electrophoretic mobility shift assays implicated FOXA as the protein. Luciferase reporter assays on rs4888378 showed a significant 35% to 92% (P=0.0057; P=4.0 × 10(-22)) decrease in gene expression with the A allele. Expression quantitative trait loci analysis confirmed previously reported associations of rs4888378 with BCAR1 in vascular tissues.


CONCLUSIONS
Molecular studies suggest the lead SNP as a potentially causal SNP at the BCAR1-CFDP1-TMEM170A locus, and expression quantitative trait loci studies implicate BCAR1 as the causal gene. This variant showed stronger effects on common carotid IMT in women, raising questions about the mechanism of the causal SNP on atherosclerosis.
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.) f.boardman-pretty.10@ucl.ac.uk.
Freya
F
Boardman-Pretty
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.).
Andrew J P
AJ
Smith
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.).
Jackie
J
Cooper
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.).
Jutta
J
Palmen
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.).
Lasse
L
Folkersen
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.).
Anders
A
Hamsten
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.).
Alberico L
AL
Catapano
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.).
Olle
O
Melander
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.).
Jacqueline F
JF
Price
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.).
Meena
M
Kumari
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.).
John E
JE
Deanfield
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.).
Mika
M
Kivimäki
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.).
Karl
K
Gertow
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.).
Andrea
A
Baragetti
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.).
Giuseppe Danilo
GD
Norata
From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimäki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmö, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.).
Steve E
SE
Humphries
D000368:Aged; D050197:Atherosclerosis / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D045744:Cell Line, Tumor; D002885:Chromosomes, Human, Pair 16; D015331:Cohort Studies; D019295:Computational Biology; D003324:Coronary Artery Disease / Q000235:genetics*; D050719:Crk-Associated Substrate Protein / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D040641:Quantitative Trait Loci; D012307:Risk Factors; D012737:Sex Factors
C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D004268:DNA-Binding Proteins; D004247:DNA
atherosclerosis; carotid intima-media thickness; coronary artery disease; genetics; polymorphism, single nucleotide