title: Period3 VNTR polymorphism influences the time-of-day pain onset of acute myocardial infarction with ST elevation.
abstract: It is well established that the incidence and infarct size in acute myocardial infarction (AMI) is subject to circadian variations. At the molecular level, circadian clocks in distinct cells, including cardiomyocytes, generate 24-h cycles of biochemical processes. Possible imbalance or impairment in the cell clock mechanism may alter the cardiac metabolism and function and increase the susceptibility of cardiovascular diseases. One of the key components of the human clock system PERIOD3 (PER3) has been recently demonstrated to affect circadian expression of various genes in different tissues, including the heart. The variable number tandem repeat (VNTR) polymorphism (rs57875989) in gene Period3 (Per3) is related to multiple phenotypic parameters, including diurnal preference, sleep homeostasis, infection and cancer. The aim of our study was to investigate the effect of this polymorphism in AMI with ST elevation (STEMI). The study subjects (314 patients of Caucasian origin with STEMI, and 332 healthy controls) were genotyped for Per3 VNTR polymorphism using an allele-specific polymerase chain reaction. A gender difference in circadian rhythmicity of pain onset was observed with significant circadian pattern in men. Furthermore, the Per3(5/5) variant carriers were associated with higher levels of interleukin-6, B-type natriuretic peptide and lower vitamin A levels. By using cosinor analysis we observed different circadian distribution patterns of AMI onset at the level of genotype and allelic frequencies. Genotypes with at least one 4-repeat allele (Per3(4/5) and Per3(4/4)) (N = 264) showed remarkable circadian activity in comparison with Per3(5/5) (N = 50), especially in men. No significant differences in genotype and/or allele frequencies of Per3 VNTR polymorphism were observed when comparing STEMI cases and controls. Our results indicate that the Per3 VNTR may contribute to modulation of cardiac functions and interindividual differences in development and progression of myocardial infarction.
authors.affiliation: Institute of Pathological Physiology, Faculty of Medicine, Masaryk University , Czech Republic .
authors.forename: Jolana
authors.initials: J
authors.lastname: Lipkova
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Splichal
authors.forename: Julie Anna
authors.initials: JA
authors.lastname: Bienertova-Vasku
authors.forename: Michal
authors.initials: M
authors.lastname: Jurajda
authors.forename: Jiri
authors.initials: J
authors.lastname: Parenica
authors.forename: Anna
authors.initials: A
authors.lastname: Vasku
authors.forename: Monika Pavkova
authors.initials: MP
authors.lastname: Goldbergova
mesh_terms: D000368:Aged; D000483:Alleles; D001794:Blood Pressure; D002940:Circadian Rhythm / Q000235:genetics; D015331:Cohort Studies; D004562:Electrocardiography; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015994:Incidence; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D009203:Myocardial Infarction / Q000235:genetics*; D056950:Period Circadian Proteins / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012890:Sleep / Q000235:genetics; D012892:Sleep Deprivation / Q000503:physiopathology
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; C512644:PER3 protein, human; D056950:Period Circadian Proteins
keywords: Circadian clock; Per3 VNTR polymorphism; cosinor analysis; heart failure; myocardial infarction