Association of Cross-Sectional and Longitudinal Change in Arterial Stiffness With Gene Expression in the Twins UK Cohort

Marina Cecelja*, Benyu Jiang, Massimo Mangino, Tim D. Spector, Phil J. Chowienczyk

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)70-76
Issue number1
Early online date16 Nov 2015
Publication statusPublished - Jan 2016


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