ABSTRACT
AIMS/HYPOTHESIS: Although genetic susceptibility plays an important role in the pathogenesis of type 2 diabetes, most of the genes that influence susceptibility to type 2 diabetes have yet to be identified. Krüppel-like transcription factors are known to play important roles in development and cell differentiation, and have recently been implicated in the pathogenesis of type 2 diabetes. The present study aimed to examine the associations of single nucleotide polymorphisms (SNPs) in genes encoding members of the Krüppel-like-factor (KLF) family with type 2 diabetes in a large cohort of Japanese subjects. METHODS: We genotyped 33 SNP loci found in 12 KLF genes in subjects with type 2 diabetes and in subjects from the general population using the PCR-Invader assay. We also examined the effects of the overexpression of KLF7 on adipogenesis in 3T3-L1 cells. RESULTS: We identified a significant association between an SNP in KLF7 and type 2 diabetes (A vs C: p=0.004 after Bonferroni's correction, odds ratio=1.59, 95% CI 1.27-2.00). The expression of Klf7 decreased in response to the differentiation of 3T3-L1 adipocytes, and the overexpression of KLF7 resulted in significant inhibition of adipogenesis in 3T3-L1 cells. CONCLUSIONS/INTERPRETATION: These results indicate that the gene encoding KLF7 is a novel candidate for conferring genetic susceptibility to type 2 diabetes.
Subject(s)
DNA-Binding Proteins/genetics , Diabetes Mellitus, Type 2/genetics , Polymorphism, Single Nucleotide , Transcription Factors/genetics , 3T3 Cells , Animals , Chromosome Mapping , Genetic Predisposition to Disease , Genotype , Humans , Introns/genetics , Kruppel-Like Transcription Factors , Mice , Multigene Family , Odds Ratio , Reference ValuesABSTRACT
In patients with acute myocardial infarction (AMI), transient QT interval prolongation with a prominent negative T wave is frequently observed in cases of early spontaneous reperfusion and often indicates a good prognosis. Additionally, in nuclear cardiac imaging, technetium-99m/thallium-201 overlap on dual single-photon emission computed tomography (dual SPECT) in AMI patients indicates the presence of viable myocardium and early recanalization. To elucidate the clinical significance of this transient QT interval prolongation, 34 patients (64 +/- 8 years) admitted within 24h of the onset of anterior AMI were enrolled and classified into 2 groups according to the presence (group A, n=24) or absence (group B, n=10) of scintigraphic overlap on simultaneous dual SPECT imaging. The maximal QTc interval was 0.59 +/- 0.06 s in group A and 0.52 +/- 0.06 s in group B (p<0.01). The peak creatine kinase was lower in group A (2650 +/- 2160 IU/L) than in group B (3490 +/- 2060 IU/L). The left ventricular ejection fraction (LVEF) at discharge was 62 +/- 11% in group A and 49 +/- 14% in group B (p<0.01). The scintigraphic overlap group had a smaller infarct and better LVEF, which suggests that the QT interval prolongation that appears transiently in the acute phase of AMI indicates scintigraphically the presence of salvaged myocardium.
