Polymorphism of the palladin gene and cardiovascular outcome in patients with atherosclerosis

• Published in: European journal of clinical investigation 2011-04, Vol.41 (4), p.365-371
• Main Authors: Hoke, Matthias, Schillinger, Martin, Dick, Petra, Exner, Markus, Koppensteiner, Renate, Minar, Erich, Mlekusch, Wolfgang, Schlager, Oliver, Wagner, Oswald, Mannhalter, Christine
• Format: Article
• Language: English
• Subjects: Aged; Alleles; Arteriosclerosis; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - complications; Atherosclerosis - genetics; Austria; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; cardiovascular outcome; Carotid Artery Diseases - genetics; Cohort Studies; Coronary Disease - genetics; Coronary heart disease; Cytoskeletal Proteins - genetics; European Continental Ancestry Group; Female; Gene polymorphism; General aspects; Genetic Predisposition to Disease; Genotype; Humans; Male; Medical sciences; Middle Aged; Myocardial infarction; palladin gene; Phosphoproteins - genetics; Polymorphism, Single Nucleotide - genetics; Prospective Studies; Risk Factors; Single-nucleotide polymorphism; Stenosis; Stroke
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2010.02416.x

Eur J Clin Invest 2011; 41 (4): 365–371 Background  A single‐nucleotide polymorphism (SNP) in the palladin gene (PALLD, rs7439293) has recently been reported to be associated with coronary heart disease (CHD) in two case–control studies as well as in a large population‐based cohort (Atherosclerosis Risk in Communities study, ARIC). Its clinical relevance, however, has not been evaluated prospectively. We investigated whether the risk allele (A) of PALLD rs7439293 (G>A) is associated with the occurrence of future major cardiovascular events (MACE) in a cohort of patients with prevalent carotid atherosclerosis. Materials and methods  A total of 1283 consecutive patients with neurologically asymptomatic carotid atherosclerosis were included in the study and prospectively followed for a median of 3·5 years (interquartile range 3–4 years). We analysed whether the risk allele is associated with progression of carotid atherosclerosis after a 6–9‐month period as measured by duplex Doppler sonography. Patients were then followed for the occurrence of a first MACE, a composite of myocardial infarction, stroke, coronary revascularization and death. Results  After a median of 7·5 months (interquartile range 6–9 months), progression of carotid stenosis was observed in 103 (8·1%) patients. Cardiovascular events occurred in 337 (30%) patients after a median follow‐up of 3·5 years. The risk allele of PALLD was neither associated with progressive carotid atherosclerosis (P = 0·21) nor with MACE (P = 0·58). Adjusted hazard ratios for a first MACE in heterozygous and homozygous carriers were 0·83 (95% CI 0·58–1·18) and 0·94 (95% CI 0·65–1·35) compared to wild type, respectively. Conclusions  The A‐allele of PALLD rs7439293 was not associated with progressive carotid atherosclerosis as measured by duplex Doppler sonography nor did it represent a risk factor for adverse cardiovascular outcome among patients with prevalent carotid atherosclerosis.