Abstract
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.
Highlights
The transcription factor encoded by the circadian locomotor output cycles kaput (CLOCK) gene is a crucial element of the molecular circadian clock [1]
The characteristics of age, insulin level, glucose level, insulin resistance, triglyceride level, high-density lipoprotein (HDL) cholesterol level, waist circumference, systolic blood pressure, diastolic blood pressure, body mass index (BMI), alcohol intake, metabolic equivalent (MET)-h/week, region, smoking status, and dietary fat composition all significantly differed by sex
1 Adjusted for age, region (Ansung, Ansan), smoking, alcohol intake (g/day), metabolic equivalent (MET)-h/week, family history of type 2 diabetes, and BMI. In this prospective cohort study, we observed an association between the minor allele carriers of the G allele (AG + GG) of CLOCK rs1801260 and the incidence of metabolic syndrome in Korean men
Summary
The transcription factor encoded by the circadian locomotor output cycles kaput (CLOCK) gene is a crucial element of the molecular circadian clock [1]. A large body of evidence suggests that genetic variation in CLOCK is associated with the development of metabolic syndrome and its components [1,3,4]. Mutations in CLOCK genes may be a causal factor for the expression of metabolic syndrome components by altering transcriptional regulation, with CLOCK mutant mice showing impaired glucose tolerance [5]. Metabolic syndrome is affected by both genetic and dietary factors. CLOCK genetic polymorphisms have been associated with metabolic syndrome, and one of the most studied CLOCK gene polymorphisms at the 3 -untranslated region is rs1801260 [7]. Dietary factors play a key role in the development of metabolic syndrome. Studies evaluating how CLOCK genetic polymorphisms predispose an individual to metabolic syndrome, and how this relationship is modulated by MUFA, are lacking
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