Genetic variations in G-protein signal pathways influence progression of coronary artery calcification: Results from the Heinz Nixdorf Recall study.

Atherosclerosis
Stefanie KlenkeJürgen Peters

Abstract

Coronary artery calcification (CAC) is one of the most sensitive and specific markers of coronary atherosclerosis and believed to be heritable. We hypothesized that functionally relevant single-nucleotide polymorphisms (SNPs) in the G-protein signal pathway, which have been previously related to coronary artery disease, are associated with CAC progression. 3108 participants from the Heinz Nixdorf Recall study with CAC measurements at both baseline (CACb) and 5-year follow-up (CAC5y) were included. We genotyped SNPs rs1042714 (ADRB2), rs6026584 and rs12481583 (GNAS), and rs5443 (GNB3) and defined a priori risk alleles derived from literature data. Regression analyses were applied to measures of 5-year CAC progression, unadjusted, adjusted for age, sex, and adjusted for age, sex, log(CACb+1) as well as for cardiovascular risk factors. The presence of one or more risk alleles was associated with a 26.9% (95% CI 5.5-52.4) increase in 5-year CAC progression (p = 0.011) and a 29.2% (95% CI 5.9-57.6) accelerated increase of CAC over the 5-year period compared to what was expected with respect to the baseline CAC percentile value (p = 0.012). Each of those risk alleles increased the 5-year CAC progression by 4.4% (95% CI 1.3-7.6, p = 0...Continue Reading

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