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
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
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DOI：
10.1007/s00109-006-0116-7
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发表时间：
2007-02-01
影响因子：
4.7
通讯作者：
Vohl, Marie-Claude
中科院分区：
文献类型：
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作者：
Robitaille, Julie;Houde, Alain;Vohl, Marie-Claude
肥胖受到遗传和营养因素的影响。目的是验证编码肉碱棕榈酰转移酶I(CPT1)的基因变异是否与肥胖表型有关，单独或与脂肪摄入量相互作用。对40例超重受试者和4例对照组进行了CPT1基因测序。对351名法裔加拿大人进行了基因分型。脂肪摄入量通过食物频率问卷进行评估。我们在CPT1a和CPT1B中发现了14个遗传变异和26个遗传变异。根据次要等位基因频率(>；10%)或潜在的功能影响，选择了CPT1B中的9个变异和CPT1A中的1个变异进行进一步分析。观察到肥胖表型(BMI、体重和腰围)与CPT1B c.282-18C>；T和p.E531K变异显著相关(p<；0.05)，未发现CPT1a和CPT1B变异的其他关联。根据E.E531K基因型别将受试者分为6组，并以脂肪为切割点(能量的34.4%)，E531/K531的体重指数、体重和腰围均高于低脂饮食的E531/K531受试者(分别为p=0.004，p=0.006，p=0.003)。E531/E531和K531/K531之间无差异。CPT1AP.A275T变异体也得到了类似的结果，因为与低脂饮食的A275/A275受试者相比，高脂肪饮食的A275/A275受试者的BMI和腰围更高。在T275等位基因携带者中，肥胖指数不受脂肪摄入量的影响(体重指数和腰围分别为p=0.05和p=0.008)。在CPT1B基因的变异中，推断出13种单倍型，其中最常见的两种单倍型H7(38.0%)和H5(27.7%)用于二倍型分析。这些单倍型与肥胖指数无关，但根据CPT1B E531K变异脂肪摄入量的观察，这种联系是调节的。总而言之，这一发现表明，肥胖指数可能受到CPT1变异和脂肪摄入量之间的相互作用的影响。
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 beta-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.