The Association between Circadian Clock Gene Polymorphisms and Metabolic Syndrome: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Metabolic syndrome is a cluster of cardio-metabolic risk factors and comorbidities, including central obesity, hypertension, hyperglycemia, and dyslipidemia. In addition, different studies have shown that the disturbances in circadian rhythm are connected with components of metabolic syndrome. Circadian rhythm is the central regulator of every aspect of human health and metabolism, and metabolic homeostasis is essential in regulating energy metabolism, especially in adipose tissue. Therefore, we aimed to evaluate the association of genetic variations of circadian rhythm genes with metabolic syndrome and its components by a systematic review and meta-analysis. Our findings suggest that some variants of the circadian rhythm gene might be genetic biomarkers applied to predict metabolic syndrome susceptibility. ABSTRACT: Metabolic syndrome (MetS) is a combination of cardiovascular risk factors associated with type 2 diabetes, obesity, and cardiovascular diseases. The circadian clock gene polymorphisms are very likely to participate in metabolic syndrome genesis and development. However, research findings of the association between circadian rhythm gene polymorphisms and MetS and its comorbidities are not consistent. In this study, a review of the association of circadian clock gene polymorphisms with overall MetS risk was performed. In addition, a meta-analysis was performed to clarify the association between circadian clock gene polymorphisms and MetS susceptibility based on available data. The PubMed and Scopus databases were searched for studies reporting the association between circadian rhythm gene polymorphisms (ARNTL, BMAL1, CLOCK, CRY, PER, NPAS2, REV-ERBα, REV-ERBβ, and RORα) and MetS, and its comorbidities diabetes, obesity, and hypertension. Thirteen independent studies were analyzed with 17,381 subjects in total. The results revealed that the BMAL1 rs7950226 polymorphism was associated with an increased risk of MetS in the overall population. In contrast, the CLOCK rs1801260 and rs6850524 polymorphisms were not associated with MetS. This study suggests that some circadian rhythm gene polymorphisms might be associated with MetS in different populations and potentially used as predictive biomarkers for MetS.