title: Association of Cross-Sectional and Longitudinal Change in Arterial Stiffness With Gene Expression in the Twins UK Cohort.
abstract: We investigated whether expression of genes previously implicated in arterial stiffening associates with cross-sectional and longitudinal measures of arterial stiffness. Women from the Twins UK cohort (n=470, aged 39-81 years) had gene expression in lymphoblastoid cell lines measured using an Illumina microarray. Arterial stiffness was measured by carotid-femoral pulse wave velocity and carotid distensibility. A subsample (n=121) of women had repeat vascular measures after a mean±SD follow-up of 4.3±1.4 years. Associations of arterial phenotypes with gene expression levels were examined for 52 genes identified from previous association studies. The gene transcript most closely associated with pulse wave velocity in cross-sectional analysis was ectonucleotide pyrophosphatase/phosphodiesterase (P=0.012). Pleiotropic genetic effects accounted for 14% of the phenotypic correlation between ectonucleotide pyrophosphatase/phosphodiesterase expression and pulse wave velocity. Progression of pulse wave velocity during the follow-up period best related to expression of ectonucleotide pyrophosphatase/phosphodiesterase (β=0.19, P=0.008) and collagen type IV α 1 (β=0.32, P<0.0001). Gene transcripts most closely related to change in carotid distensibility during the follow-up period were endothelial nitric oxide synthase (β=-0.20, P=0.005), angiotensin-converting enzyme (β=-0.15, P=0.035), and B-cell CLL/lymphoma11B (β=0.18, P=0.010). Expression levels of angiotensin-converting enzyme also related to progression in carotid diameter (β=0.21, P=0.012). Expression levels of ectonucleotide pyrophosphatase/phosphodiesterase, involved in arterial calcification, and collagen type IV α 1, involved in collagen formation, correlate with aortic stiffening. These genes may be functional mediators of arterial stiffening.
authors.affiliation: From the Cardiovascular Division, Department of Clinical Pharmacology, King's College London British Heart Foundation Centre (M.C., B.Y., P.J.C.) and Department of Twin Research and Genetic Epidemiology, King's College London (M.M., T.D.S.), St. Thomas' Hospital, London, United Kingdom; and NIHR Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London, United Kingdom (M.M.).
authors.forename: Marina
authors.initials: M
authors.lastname: Cecelja
authors.affiliation: From the Cardiovascular Division, Department of Clinical Pharmacology, King's College London British Heart Foundation Centre (M.C., B.Y., P.J.C.) and Department of Twin Research and Genetic Epidemiology, King's College London (M.M., T.D.S.), St. Thomas' Hospital, London, United Kingdom; and NIHR Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London, United Kingdom (M.M.).
authors.forename: Benyu
authors.initials: B
authors.lastname: Jiang
authors.affiliation: From the Cardiovascular Division, Department of Clinical Pharmacology, King's College London British Heart Foundation Centre (M.C., B.Y., P.J.C.) and Department of Twin Research and Genetic Epidemiology, King's College London (M.M., T.D.S.), St. Thomas' Hospital, London, United Kingdom; and NIHR Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London, United Kingdom (M.M.).
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.affiliation: From the Cardiovascular Division, Department of Clinical Pharmacology, King's College London British Heart Foundation Centre (M.C., B.Y., P.J.C.) and Department of Twin Research and Genetic Epidemiology, King's College London (M.M., T.D.S.), St. Thomas' Hospital, London, United Kingdom; and NIHR Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London, United Kingdom (M.M.).
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: From the Cardiovascular Division, Department of Clinical Pharmacology, King's College London British Heart Foundation Centre (M.C., B.Y., P.J.C.) and Department of Twin Research and Genetic Epidemiology, King's College London (M.M., T.D.S.), St. Thomas' Hospital, London, United Kingdom; and NIHR Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London, United Kingdom (M.M.). phil.chowienczyk@kcl.ac.uk.
authors.forename: Phil J
authors.initials: PJ
authors.lastname: Chowienczyk
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001161:Arteriosclerosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology; D003430:Cross-Sectional Studies; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D063177:Pulse Wave Analysis; D014427:Twins / Q000235:genetics*; D014463:Ultrasonography; D006113:United Kingdom; D059289:Vascular Stiffness / Q000502:physiology*
keywords: aging; gene expression; longitudinal studies; twins; vascular stiffness