Gene associated with artery elasticity linked to increased risk of CAD

Susan Jeffrey

August 05, 2002

Mon, 05 Aug 2002 20:00:00

Dallas, TX - Dutch researchers report that a specific mutation of the ABCC6 genepreviously shown to cause a connective tissue disorder with cardiovascular complicationsis strongly associated with the presence of premature coronary artery disease. A large case-control study showed that prevalence of the R1141X mutation of the gene was 4 times higher among CAD cases than among healthy controls. The new finding is published in the August 6, 2002 rapid access issue of Circulation.

"We could not find a relation between this mutation and other major CAD risk factors, suggesting this mutation in the ABCC6 transporter is operating through a novel pathway of atherogenesis," the researchers, led by Dr Mieke D Trip (University of Amsterdam, the Netherlands), write.

PXE link

This group and others have recently shown that mutations in the ATP-binding cassette (ABC) transporter gene (ABCC6) cause a disorder called pseudoxanthoma elasticum (PXE), which is characterized by deranged metabolism of elastic fibers. The resulting changes affect the eyes, skin, gastrointestinal tract, and the cardiovascular system, the authors write. Cardiovascular changes include premature CAD, cerebrovascular disease, peripheral vascular disease, and renal hypertension. The hallmark of the disorder is dystrophic mineralization of the skin, retina, and arterial walls.

While mutations in the ABCC6 gene have been shown to cause PXE, Trip et al point out, the exact function of this gene is still not known, nor is the precise relationship between mutations in the ABCC6 gene and the expression of PXE.

However, given some of the systemic effects seen in PXE, Trip et al hypothesized that a single ABCC6 gene mutation on one allele (ie, being heterozygous for the mutation) may confer an increased risk for CAD among the general population. In this study, they compared prevalence of the R1141X mutation in a group of 441 patients with premature CAD (defined as definite CAD before age 50) with that in a population-based group of 1057 age- and sex-matched controls free of CAD.

"Strikingly, the prevalence of the R1141X mutation was 4.2 times higher among patients than among controls," Trip and colleagues write.

Prevalence of the R1141X mutation in CAD patients and healthy controls


CAD patients


p value

14 (3.2)
8 (0.8)
To download table as a slide, click on the slide logo below

Among those with the mutation, the odds ratio for a coronary event was 4.23 (95% CI 1.76-10.20, p=0.001).

"Whatever the specific pathophysiology of PXE, our study results seem to indicate that mutations in the ABCC6 gene are not rare in the general population and contribute to an increased propensity toward premature atherosclerotic vascular disease," Trip et al conclude. "If our data are subsequently confirmed in other cohorts, this might have implications for genetic screening in PXE kindreds and may require a more aggressive approach toward CAD prevention in these individuals."

Related links

1. [HeartWire > News; Feb 28, 2002]


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