title: Resequencing the untranslated regions of the lipoprotein lipase (LPL) gene reveals that variants in microRNA target sequences are associated with triglyceride levels.
abstract: BACKGROUND
  Rare variants in the protein coding regions of the lipoprotein lipase (LPL) gene have been shown to be important in the development of hypertriglyceridemia.
  
  
  OBJECTIVE
  The aim of this study was to determine whether rare variants in the 3' and 5' untranslated regions (UTRs) of the LPL gene are also associated with severe hypertriglyceridemia.
  
  
  METHODS
  The DNA sequences of the 3' and 5' UTRs of the LPL gene of 63 patients with triglycerides > 875 mg/dL (10 mmol) and 69 probands with triglycerides below the 25th percentile for age and sex were determined. The sequence at the 5' end was extended to include 2 further elements (-702 to -666 and -468 to -430) shown to be associated with the control of LPL expression.
  
  
  RESULTS
  No statistically significant difference was found in the occurrence of rare mutations in either the 3' or the 5' UTRs between the 2 groups. Sequence analysis allowed the genotyping of 47 single nucleotide polymorphisms (SNPs) in the 3' UTR and 11 in the 5' UTR. Two groups of SNPs in the 3' UTR, based on allelic association, were statistically significantly associated with plasma triglycerides. Each of these groups contained SNPs in the target sequences for microRNAs. These findings were replicated in independently formed groups.
  
  
  CONCLUSIONS
  We provide genetic evidence that microRNAs may play a role in the expression of LPL and thus plasma triglyceride levels.
authors: Endokrinologie und Stoffwechsel, Medizinische Klinik III, Zentrum für Innere Medizin, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Electronic address: evans@uke.uni-hamburg.de.
authors: David
authors: D
authors: Evans
authors: Frank Ulrich
authors: FU
authors: Beil
authors: Jens
authors: J
authors: Aberle
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D005260:Female; D005838:Genotype; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics / Q000473:pathology; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014280:Triglycerides / Q000097:blood*
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D035683:MicroRNAs; D014280:Triglycerides; D008071:Lipoprotein Lipase
keywords: Hypertriglyceridemia; Lipoprotein lipase; MicroRNA; Resequencing