Polymorphism in the CLOCK gene may influence the effect of fat intake reduction on weight loss

Nutrition. 2016 Apr;32(4):453-60. doi: 10.1016/j.nut.2015.10.013. Epub 2015 Nov 6.


Objectives: The aim of this study was to assess the effect of a weight loss treatment on obesity- associated variables with respect to the CLOCK and FTO genotypes.

Methods: In all, 179 volunteers (78% female) participated in a 12-week calorie-restriction program; hypocaloric diets of between 5442 and 10048 kJ/d were individually prescribed to all participants. Dietetic, anthropometric, and biochemical data were collected at baseline and at the end of the intervention. When treatment was over, five single nucleotide polymorphisms (SNPs) were sought in CLOCK and FTO in all participants who provided consent. Bonferroni-corrected linear regression models were used to examine the influence of interactions of the type genotype × dietetic change on obesity-associated variables.

Results: Variation in the CLOCK and FTO genotypes had no significant influence on the change in obesity-associated variables. The interaction genotype × percentage intake of dietary fat had a significant influence on body mass index (BMI; adjusted P = 0.03). Participants carrying CLOCK rs3749474 (TT + CT) showed a positive association between the change in percentage intake of dietary fat and change in BMI (β = 0.044; 95% confidence interval [CI], 0.0119-0.0769; P = 0.008), whereas participants homozygous for the wild-type allele (CC) showed a negative, although nonsignificant association (β = -0.032; 95% CI, -0.0694 to 0.036; P = 0.077).

Conclusion: The possession of CLOCK rs3749474 may influence the effect of reducing the percentage intake of dietary fat on obesity-associated variables. Participants carrying this SNP might benefit more than others from weight loss treatment involving dietary fat restriction. The treatment of obesity might therefore be customized, depending on the alleles carried.

Keywords: CLOCK; Gene–diet interaction; Nutrigenetics; Obesity; rs3749474.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / metabolism
  • Apolipoprotein A-I / blood
  • Apolipoproteins B / blood
  • Blood Glucose / metabolism
  • Body Mass Index
  • CLOCK Proteins / genetics*
  • CLOCK Proteins / metabolism
  • Caloric Restriction*
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Dietary Carbohydrates / administration & dosage
  • Dietary Carbohydrates / analysis
  • Dietary Fats / administration & dosage*
  • Dietary Fats / analysis
  • Dietary Proteins / administration & dosage
  • Dietary Proteins / analysis
  • Energy Intake
  • Exercise
  • Female
  • Gene-Environment Interaction
  • Humans
  • Insulin Resistance
  • Male
  • Nutrition Assessment
  • Obesity / diet therapy
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide
  • Triglycerides / blood
  • Weight Loss / genetics*


  • Apolipoprotein A-I
  • Apolipoproteins B
  • Blood Glucose
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Dietary Carbohydrates
  • Dietary Fats
  • Dietary Proteins
  • Triglycerides
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human
  • CLOCK Proteins
  • CLOCK protein, human