P54Per3 VNTR polymorphism and expression in acute myocardial infarction with sT elevation

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Abstract

Human autonomic processes such as the control of sleep, body temperature, hormone secretion, renal and cardiovascular functions are influenced by circadian variations. There is obvious diurnal variation in blood pressure, heart rate and cardiac output; moreover, it has been known for long time that the fatal cardiovascular events occur preferentially in certain time of the day. Molecular clocks present in individual cells consist of clock genes and their resultant proteins that generate self-sustained transcriptional feedback loops with a free-running period of 24h. One of the key components of the human clock system, Period 3 (Per3), has been recently demonstrated to affect circadian expression of various genes in different tissues including heart. Possible imbalance or impairment in clock mechanism within the cardiomyocytes may alter the cardiac metabolism and function and thus increase the susceptibility of cardiovascular diseases.

The aim of our study was to investigate the effect of variable number tandem repeat (VNTR) polymorphism in Per3 gene in acute myocardial infarction with ST elevation (STEMI). The study subjects (336 patients of Caucasian origin with STEMI, and 332 healthy controls) were genotyped for Per3 VNTR polymorphism using an allele-specific PCR. PER3 quantification of mRNA from circulation was performed using quantitative real-time polymerase chain reaction (qRT-PCR). The follow-up of PER3 expression in 10 patients within interval of 8 hours was carried out (6 samples per patient). Within the STEMI patients, the difference in allelic frequencies of Per3 VNTR polymorphism was observed when comparing the time of MI onset (pa = 0.01). The long variant (5/5) of Per3 VNTR polymorphism was more common within STEMI patients with pain onset during the night hours (p = 0.045). A trend of higher PER3 expression in short variant (4/4) was observed (p = 0.08). The lowest expression was found in time of MI onset with increasing PER3 expression in following hours. No significant differences in genotype and/or allele frequencies of Per3 VNTR polymorphism were observed when comparing STEMI cases and control group. In the multivariate regression modelling, no predictive function of VNTR Per3 polymorphism on ejection fraction, hyperlipidaemia or type II diabetes risk was observed.

Based on the results of the presented study, we consider a possible effect of the Per3 VNTR long variant on time of the pain onset during MI in STEMI patients.

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