Association of Cross-Sectional and Longitudinal Change in Arterial Stiffness With Gene Expression in the Twins UK Cohort. Issue 1 (January 2016)

• Record Type: Journal Article
• Authors: Cecelja, Marina; Jiang, Benyu; Mangino, Massimo; Spector, Tim D.; Chowienczyk, Phil J.
• Is Part Of: Hypertension. Volume 67:Issue 1(2016:Jan.)
• Publication Date: 2016-01
• Subjects: aging -- gene expression -- longitudinal studies -- twins -- vascular stiffness; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.115.05802
• Languages: English
• ISSNs: 0194-911X

Abstract

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. Abstract : Supplemental Digital Content is available in the text.