CLOCK Gene Variation Is Associated with the Incidence of Metabolic Syndrome Modulated by Monounsaturated Fatty Acids

The circadian locomotor output cycles kaput (CLOCK) gene plays a crucial role in regulating circadian rhythms through its transcription factor gene product. The objective of this study was to investigate the association between CLOCK rs1801260 and the incidence of metabolic syndrome modulated by dietary monounsaturated fatty acid (MUFA) intake in Korean adults. Using a dataset from the Ansan-Ansung Cohort Study of the Korean Genome and Epidemiology Study, 3608 Korean adults were included after an average of nine years of follow-up. Men who were minor allele carriers (G allele) of CLOCK rs1801260 had a 18% higher incidence of metabolic syndrome than non-carriers [hazard ratio (HR), 1.18; 95% confidence interval (CI), 1.00-1.40; p Value = 0.047]. By dichotomizing dietary MUFA intake, we observed that men who were minor allele carriers (G allele) of CLOCK rs1801260 had a 42% increased incidence of metabolic syndrome when dietary MUFA intake was <= 3.5% (HR: 1.42, 95% CI 1.23-1.81; p Value = 0.004). No significant association was found between CLOCK rs1801260 and the incidence of metabolic syndrome modulated by dietary MUFA intake in women. CLOCK polymorphisms affected metabolic syndrome, modulated by dietary MUFA intake in men. These results suggest the significance of CLOCK genes in the pathogenesis of metabolic syndrome and the modulating role of dietary MUFA intake and provide new insights into the underlying mechanisms connecting the circadian system, dietary factors, and metabolic syndrome.