Polymorphic Appetite Effects on Waist Circumference Depend on rs3749474 CLOCK Gene Variant

Nutrients. 2020 Jun 21;12(6):1846. doi: 10.3390/nu12061846.


Chronobiological aspects controlled by CLOCK genes may influence obesity incidence. Although there are studies that show an association between the expression of these genes and energy intake, waist circumference or abdominal obesity phenotypes, interactions with appetite have been insufficiently investigated in relation to chrononutrition. The objective was to identify interactions between CLOCK genetic variants involved in appetite status. A total of 442 subjects (329 women, 113 men; aged 18 to 65 years) were recruited. Anthropometric, dietary and lifestyle data were collected by trained nutritionists. Participants were classified according to their appetite feelings with a Likert scale. Multiple linear regression models were used to examine associations of the type genotype x appetite status on adiposity-related variables. p values were corrected by the Bonferroni method. A significant influence was found concerning the effects of appetite on waist circumference with respect to rs3749474 CLOCK polymorphism (p < 0.001). An additive model analysis (adjusted by age, gender, exercise and energy intake) showed that risk allele carriers, increased the waist circumference around 14 cm (β = 14.1, CI = 6.3-22.0) by each increment in the level of appetite. The effects of appetite on waist circumference may be partly modulated by the rs3749474 CLOCK polymorphism.

Keywords: biorhythm genes; chronobiology; interaction; metabolic syndrome; obesity; polymorphism.

MeSH terms

  • Abdominal Fat / metabolism*
  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Appetite Regulation
  • Appetite*
  • CLOCK Proteins / genetics*
  • Chronobiology Phenomena
  • Circadian Rhythm / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity, Abdominal / etiology
  • Obesity, Abdominal / genetics*
  • Obesity, Abdominal / metabolism
  • Polymorphism, Genetic*
  • Waist Circumference*
  • Young Adult


  • CLOCK Proteins
  • CLOCK protein, human