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Circadian Rhythm Gene Polymorphisms and Susceptibility to Metabolic Syndrome: a Meta- Analysis

Introduction: Metabolic syndrome (MetS) is a set of cardiovascular risk factors associated with type 2 diabetes, obesity, and cardiovascular diseases. Research findings of the association between circadian rhythm gene polymorphisms and MetS and its comorbidities are not consistent. This meta-analysis was performed to quantify the relationships between circadian rhythm genes and the risk of MetS. Materials and Methods: The PubMed and Scopus databases were searched for studies reporting on the association between circadian rhythm gene polymorphisms (ARNTL, BMAL1, CLOCK, CRY, PER, NPAS2, RORα, REV-ERBα, and REV- ERBβ) and MetS, and its comorbidities type 2 diabetes, obesity, and hypertension. A random- effect model was used to calculate the pooled odds ratio and 95% confidence interval by comprehensive meta-analysis software. Results: Eleven independent studies were analyzed with 16, 431 subjects in total. The meta-analysis revealed a significant association between circadian rhythm gene polymorphisms and MetS (OR = 1.19, 95% CI: 1.04–1.38, p = 0.013). The subgroup analysis on comorbidity related to MetS revealed that type 2 diabetes was associated with circadian rhythm genes (OR = 1.07, 95% CI: 1.00–1.14, p = 0.04). Furthermore, the subgroup analyses revealed that BMAL1 and CLOCK genes were associated with MetS (OR = 1.26, 95% CI: 1.05–1.52, p = 0.014, and OR = 1.49, 95% CI: 1.23–1.80, p < 0.001, respectively) with significant heterogeneity (I2 = 75.3%, p = 0.001). Conclusion: This study suggests that circadian rhythm gene polymorphisms might be associated with MetS and its comorbidity and potentially cause cardiovascular diseases. Grant no. IP8-FDMZ-2020

circadian rhythm genes ; type 2 diabetes mellitus ; hypertension ; metabolic syndrome ; obesity

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