Abstract
Obesity is under the influence of genetic and nutritional factors. The objective was to verify whether variants in the gene encoding the carnitine palmitoyltransferase I (CPT1), a key enzyme in β-oxidation of fatty acids, are associated with obesity phenotypes, alone or in interaction with fat intake. Sequencing of CPT1 was performed in 40 overweight subjects and 4 controls. Genotypes were determined in 351 French-Canadians. Fat intake was evaluated by a food frequency questionnaire. We identified 14 genetic variations in CPT1A and 26 in CPT1B. Nine variants within CPT1B and one variant within CPT1A were selected for further analyses based on the minor allele frequency (>10%) or on potential functional impact. A significant association between obesity phenotypes (BMI, weight, and waist girth) and CPT1B c.282-18C > T and p.E531K variants was observed (p < 0.05) No other association was found with variants in CPT1A and CPT1B. When subjects were divided into six groups according to p.E531K genotypes and further on the basis of fat using the median value as a cutoff point (34.4% of energy), BMI, weight, and waist girth were higher in E531/K531 on a high-fat diet compared to E531/K531 subjects under a low-fat diet (p = 0.004, p = 0.006, p = 0.003, respectively). There was no difference among E531/E531 and K531/K531. Similar results were obtained with the CPT1A p.A275T variant as BMI and waist girth were higher in A275/A275 on a high fat compared to A275/A275 subjects on a low-fat diet. Among carriers of the T275 allele, obesity indices were not affected by fat intake (p = 0.05 and p = 0.008 for BMI and waist girth, respectively). Among variants within the CPT1B gene, 13 haplotypes were inferred and the two most frequent haplotypes, H7 (38.0%) and H5 (27.7%), were kept for diplotype analysis. These haplotypes were not associated with indices of obesity, but as observed with the CPT1B E531K variant fat intake modulated this association. In conclusion, this finding suggests that indices of obesity might be modulated by an interaction between CPT1 variants and fat intake.
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Acknowledgements
The authors would like to acknowledge the contribution of the staffs of the CHUL Lipid Research Center and the Lipid Clinic, as well as the Department of Biochemistry and the Cardiology Service of the Chicoutimi Hospital for their dedicated support and assistance. The authors would like to express their gratitude to the subjects for their excellent collaboration.
This study was supported by a grant from the Canadian Institutes of Health Research (MOP-44074) and the Heart and Stroke Foundation of Canada. J. Robitaille received a doctoral studentship from the Canadian Institutes of Health Research. M.C. Vohl and S. Lemieux are research scholars from the “Fonds de la recherche en santé du Québec (FRSQ).” D. Gaudet is the chairholder of the Canada Research Chair in preventive genetics and community genomics (http://www.chaires.gc.ca).
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Robitaille, J., Houde, A., Lemieux, S. et al. Variants within the muscle and liver isoforms of the carnitine palmitoyltransferase I (CPT1) gene interact with fat intake to modulate indices of obesity in French-Canadians. J Mol Med 85, 129–137 (2007). https://doi.org/10.1007/s00109-006-0116-7
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DOI: https://doi.org/10.1007/s00109-006-0116-7