Department of Microbiology and Biotechnology, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Hermann-Weigmann-Strasse 1, D-24103 Kiel, Germany.
Br J Nutr. 2013 Mar 14;109(5):810-5. doi: 10.1017/S0007114512002656. Epub 2012 Jul 19.
The carnitine palmitoyltransferase (CPT) enzyme system facilitates the transport of long-chain fatty acids into mitochondria to provide substrates for β-oxidation. We performed an analysis including three coding SNP in the muscle isoform of the CPT1b gene (rs3213445, rs2269383 and rs470117) and one coding SNP in the CPT2 gene (rs1799821) to find associations with traits of the metabolic syndrome (MetS). Male participants (n 755) from the Metabolic Intervention Cohort Kiel were genotyped and phenotyped for features of the MetS. Participants underwent a glucose tolerance test and a postprandial assessment of metabolic variables after a standardised mixed meal. Carriers of the rare CPT1b 66V (rs3213445) allele had significantly higher γ-glutamyl transpeptidase (GGT), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvate transaminase (GPT) activities (P< 0·0001, P= 0·03 and P= 0·048, respectively) and a higher fatty liver index (FLI, P= 0·026). Fasting and postprandial TAG (P= 0·007 and P= 0·009, respectively) and fasting glucose (P= 0·012) were significantly higher in 66V-allele carriers. The insulin sensitivity index determined after a glucose load was lower in those subjects (P= 0·005). Total cholesterol (P= 0·051) and LDL-cholesterol (P= 0·062) tended to be higher in 66V-allele carriers when compared with I66I homozygotes. Homozygosity of the rare K531E allele presented with lower GGT and GOT activities (P= 0·011 and P= 0·027, respectively). E531E homozygotes tended to have lower GPT and FLI (P= 0·078 and P= 0·052, respectively). CPT2 V368I (rs1799821) genotypic groups did not differ in the investigated anthropometric and metabolic parameters. The present results confirm the association of CPT1b coding polymorphisms with the MetS, with a deleterious effect of the CPT1b I66V and a protective impact of the CPT1b K531E SNP, whereas haplotype analysis indicates a relevance of the E531K polymorphism only.
肉碱棕榈酰基转移酶（CPT）酶系统促进长链脂肪酸向线粒体的转运，为β-氧化提供底物。我们进行了一项分析，包括肌肉同工型 CPT1b 基因中的三个编码 SNP（rs3213445、rs2269383 和 rs470117）和 CPT2 基因中的一个编码 SNP（rs1799821），以寻找与代谢综合征（MetS）特征相关的关联。代谢干预队列基尔的男性参与者（n=755）进行了基因分型和代谢综合征特征的表型分析。参与者接受了葡萄糖耐量试验和标准混合餐后的餐后代谢变量评估。罕见的 CPT1b 66V（rs3213445）等位基因携带者的γ-谷氨酰转肽酶（GGT）、谷草转氨酶（GOT）和谷丙转氨酶（GPT）活性显著升高（P<0·0001、P=0·03 和 P=0·048，分别）和更高的脂肪肝指数（FLI，P=0·026）。空腹和餐后 TAG（P=0·007 和 P=0·009，分别）和空腹血糖（P=0·012）在 66V-等位基因携带者中显著升高。负荷后胰岛素敏感性指数（ISI）较低（P=0·005）。与 I66I 纯合子相比，66V 等位基因携带者的总胆固醇（P=0·051）和 LDL 胆固醇（P=0·062）水平也倾向于升高。罕见的 K531E 等位基因纯合子的 GGT 和 GOT 活性较低（P=0·011 和 P=0·027，分别）。E531E 纯合子的 GPT 和 FLI 水平较低（P=0·078 和 P=0·052，分别）。CPT2 V368I（rs1799821）基因型组在研究的人体测量和代谢参数方面没有差异。本研究结果证实了 CPT1b 编码多态性与 MetS 的关联，CPT1b I66V 具有有害作用，CPT1b K531E SNP 具有保护作用，而单体型分析仅表明 E531K 多态性的相关性。
