Cardiomyopathy and carnitine deficiency
Section snippets
Materials and methods
The protocol for DNA studies was approved by the University of Colorado and by the University of Utah Institutional Review Board. Informed consent was obtained from all patients or their parents prior to DNA studies. GenBank sequence AB016625.1 was used as reference for the gene, NM_003060.2 was used as the reference sequence for the cDNA. Genomic DNA was obtained from 324 patients with cardiomyopathy part of the cardiomyopathy registry [14], [15]. About 10% of these patients had hypertrophic
Results
Direct DNA sequencing of exon 1 of the SLC22A5 gene did not identify any significant variation in the DNA of patients with cardiomyopathy. Screening of the remaining exons (2–10) of the SLC22A5 gene by high-resolution melting analysis in 324 patients with cardiomyopathy identified 38 variants out of 2916 exons screened. An example of the melting curve of selected exons is shown in Fig. 1. DNA sequencing identified polymorphisms not affecting the amino acid residues and described in the normal
Discussion
Primary carnitine deficiency impairs the accumulation of carnitine within organs and tissues [9]. In the heart, carnitine is essential for normal fatty acid β-oxidation and even partial deficiency could lead to organ dysfunction. Heterozygous animal models of primary carnitine deficiency have a higher rate of cardiomyopathy with aging [11], [12]. Humans heterozygous for primary carnitine deficiency have mildly reduced plasma carnitine levels due to increased urinary losses [8] and might develop
Acknowledgments
We thank Idaho Technology Inc. for allowing the use of the HR-1 High-Resolution Melter and for valuable help in optimizing the screening assay. We also thank the Familial Cardiomyopathy Study subjects for their participation. This study was supported by Grant-in-Aid 0455086Y from the American Heart Association and in part by Grants DK 53824 and 1K23Hl67915-01A1 from the National Institutes of Health.
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2017, Advanced Drug Delivery ReviewsCitation Excerpt :Eight genetic variants of OCTN2 were found to have altered transport activity in the uptake of TEA and/or L-carnitine. Grube et al. indicated that OCTN2 expression is selectively reduced in dilated cardiomyopathy patients [220], although the frequency of OCTN2 variants identified in patients with cardiomyopathy were not different from that of the normal people [217]. This suggested the presence of possible polymorphisms of OCTN2 gene within the promoter region.
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Cardiovascular System
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