Neuropeptide Y signal peptide Pro7 substitution protects against coronary artery atherosclerosis: the Helsinki Sudden Death Study.

OBJECTIVE

Neuropeptide Y (NPY) has a single nucleotide polymorphism at T1128C, leading to change of Leucine7 to Proline7. The Leu7Pro substitution has been linked to cardiovascular disease, but it is unknown whether the Pro7 allele is associated with increased or decreased risk of coronary heart disease (CHD). The aim of the present study was to investigate the association of the Leu7Pro polymorphism with coronary atherosclerosis and its consequences.

METHODS

We studied two autopsy series comprising 700 unselected middle-aged Caucasian men (Helsinki Sudden Death Study) who had died suddenly out of hospital. Areas of coronary artery atherosclerosis, narrowings of coronary arteries, and presence of myocardial infarction and/or coronary thrombosis were analyzed. All information including CHD risk factor data was obtained from 410 men.

RESULTS

NPY genotype distribution was Leu7/Leu7=89.8%, Leu7/Pro7=10.0% and Pro7/Pro7=0.2%). Although the Pro7 allele was associated with reported hypertension (p=0.03), the men carrying Pro7 allele had lower area of fatty streaks (p=0.04), fibrotic lesions (p=0.07) and complicated lesions (p=0.004) in the left anterior descending (LAD) coronary artery and also less severe LAD narrowings (p=0.04) than men with the Leu7/Leu7 genotype. Supporting a protective role for the Pro7 allele against atherosclerosis, only 1 out of 46 men (2%) with coronary thrombosis carried the Pro7 allele (p=0.08 compared to men dying of other causes). This association weakened (OR 0.18 for Pro7 versus Leu7/Leu7, p=0.16) when adjusted for all available CHD risk factors.

CONCLUSIONS

NPY Pro7 substitution protects middle-aged men from coronary artery atherosclerosis and might decrease the risk of acute coronary events.