The association of the cardiovascular disease with the T3111C polymorphism in the CLOCK gene

Cardiovascular diseases (CVDs) are among the leading causes of death worldwide, although CVDs mortality has decreased in developed countries. Numerous pathophysiological processes lead to the development of CVDs. The circadian rhythm coordinates many physiological processes, and its disruption can lead to many pathophysiological changes. One of the significant circadian rhythm genes is the CLOCK gene, whose polymorphisms are associated with CVD risk factors. Research findings of the association between CLOCK gene polymorphism and CVDs and its comorbidities are not consistent. This meta-analysis was conducted to quantify the associations between T3111C polymorphism and the risk of CVDs. The PubMed and Scopus databases were searched for studies reporting on the association between T3111C (rs1801260) in the circadian CLOCK gene and cardiovascular disease and its comorbidities such as obesity, hypertension, insulin resistance, and coronary artery disease. A fixed-effect model was used to calculate the pooled odds ratio and 95% confidence interval by comprehensive meta-analysis software. Five independent studies, including case-control, cross-sectional, and cohort research methods, were analyzed with 3,123 subjects in total. The meta-analysis revealed a significant association between T3111C polymorphism and cardiovascular disease (OR = 1.32, 95% CI: 1.16–1.50, p < 0.001) with significant heterogeneity (I2 = 91.1%, p < 0.001) and no publication bias. The subgroup analysis on comorbidity related to CVDs revealed that hypertension was associated with T3111C polymorphism (OR = 2.02, 95% CI: 1.60–2.54, p < 0.001). Our meta-analysis based on available studies using a fixed model shows that T3111C polymorphism in the CLOCK gene is associated with CVDs susceptibility. This research was funded by a grant from the Croatian Ministry of Science and Education and dedicated to multi-year institutional financing of scientific activity at the Josip Juraj Strossmayer University of Osijek, Osijek, Croatia grant number IP8-FDMZ-2020.