title: Lack of association of CPT1A polymorphisms or haplotypes on hepatic lipid content or insulin resistance in Japanese individuals with type 2 diabetes mellitus.
abstract: 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.
authors: Division of Diabetes and Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. hirota@med.kobe-u.ac.jp
authors: Yushi
authors: Y
authors: Hirota
authors: Takeshi
authors: T
authors: Ohara
authors: Masako
authors: M
authors: Zenibayashi
authors: Shin-ichi
authors: S
authors: Kuno
authors: Keiko
authors: K
authors: Fukuyama
authors: Tetsuya
authors: T
authors: Teranishi
authors: Kunichi
authors: K
authors: Kouyama
authors: Kazuaki
authors: K
authors: Miyake
authors: Eiichi
authors: E
authors: Maeda
authors: Masato
authors: M
authors: Kasuga
mesh_terms: D000368:Aged; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D005234:Fatty Liver / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D005260:Female; D006239:Haplotypes; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D007564:Japan; D015810:Linkage Disequilibrium; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood
chemical_list: D014280:Triglycerides; D004247:DNA; D002334:Carnitine O-Palmitoyltransferase