Hirota Yushi, Ohara Takeshi, Zenibayashi Masako, Kuno Shin-ichi, Fukuyama Keiko, Teranishi Tetsuya, Kouyama Kunichi, Miyake Kazuaki, Maeda Eiichi, Kasuga Masato
Division of Diabetes and Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Metabolism. 2007 May;56(5):656-61. doi: 10.1016/j.metabol.2006.12.014.
Accumulation of fat in the liver is associated with insulin resistance and type 2 diabetes mellitus. The carnitine palmitoyltransferase (CPT) enzyme system facilitates the transport of long-chain fatty acids into mitochondria, and the gene for the hepatic isoform of CPT1 (CPT1A) is a candidate gene for metabolic disorders such as insulin resistance associated with fatty liver. We have now investigated the contribution of the CPT1A locus to hepatic lipid content (HLC), insulin resistance, and susceptibility to type 2 diabetes mellitus. A total of 324 type 2 diabetic patients and 300 nondiabetic individuals were enrolled in the study. Eighty-seven of the type 2 diabetic patients who had not been treated with insulin or lipid-lowering drugs were evaluated by homeostasis model assessment for insulin resistance and were subjected to nuclear magnetic resonance for determination of HLC. A total of 19 single nucleotide polymorphisms (SNPs) were identified at the CPT1A locus, and linkage disequilibrium analysis revealed a strong linkage disequilibrium block between SNP8 (intron 5) and SNP17 (intron 14). Neither haplotypes nor SNPs of CPT1A were found to be associated either with susceptibility to type 2 diabetes mellitus or with HLC or insulin resistance in type 2 diabetic patients.
肝脏中脂肪的积累与胰岛素抵抗和2型糖尿病有关。肉碱棕榈酰转移酶（CPT）酶系统促进长链脂肪酸进入线粒体，CPT1肝脏同工型（CPT1A）的基因是诸如与脂肪肝相关的胰岛素抵抗等代谢紊乱的候选基因。我们现在研究了CPT1A基因座对肝脏脂质含量（HLC）、胰岛素抵抗和2型糖尿病易感性的影响。共有324名2型糖尿病患者和300名非糖尿病个体参与了该研究。对87名未接受胰岛素或降脂药物治疗的2型糖尿病患者进行了稳态模型评估以检测胰岛素抵抗，并进行了核磁共振以测定HLC。在CPT1A基因座共鉴定出19个单核苷酸多态性（SNP），连锁不平衡分析显示SNP8（内含子5）和SNP17（内含子14）之间存在强连锁不平衡块。在2型糖尿病患者中，未发现CPT1A的单倍型或SNP与2型糖尿病易感性、HLC或胰岛素抵抗相关。
