Circadian CLOCK Gene Variants, Parameters of Arterial Stiffness and Blood Pressure Levels in Subjects Without Arterial Hypertension

Abstract

CLOCK gene polymorphic variants, parameters of arterial stiffness and blood pressure (BP) variability were studied in 115 normotensive Russian patients without cardiovascular diseases (62 men, 53 women; mean age 36.4+/-1.01 years). Examination included ECG, 24h BP monitoring, duplex scan of carotid arteries, registration of vascular stiffness parameters, and genotyping of the following polymorphic markers of CLOCK: 3111T>C (3-untranslated region), 862T>C (exon 9) and 257T>G (promoter region) by PCR-RFLP method. Pulse wave velocity was not significantly different among carriers of various 257T>G, 862T>C, 3111T>C genotypes. Augmentation index (Aix night, Aix max) values were lower in individuals with genotypes allegedly associated with essential hypertension and ischemic heart disease (257GG, 862CC, 3111CC). Arterial stiffness index (ASI) was significantly higher in men having CC genotype of 862T>C. Polymorphic variants 257T>G and 862T>C SNPs of CLOCK gene were found to be associated with parameters reflecting BP variability (morning rise of diastolic BP and rate of BP rise). These results provide a basis for suggestion that the CLOCK gene polymorphism is one of factors determining elastic properties of vascular wall. The suggestion is supported by discussion of possible molecular mechanisms of circadian genes impact on elasticity and rigidity of vessel.