title: The variation of the sarcolipin gene (SLN) in atrial fibrillation, long QT syndrome and sudden arrhythmic death syndrome.
abstract: BACKGROUND
  Mutations in genes responsible for the cardiac action potential and control of intracellular Ca(2+)-distribution are associated with cardiac arrhythmia and sudden death. Sarcolipin is a 31-amino acid protein that inhibits the sarcoplasmic reticulum Ca(2+) ATPase pump (SERCA2). The sarcolipin gene, SLN, is expressed in the heart and a candidate gene for cardiomyopathy as well as atrial fibrillation (AF), long QT syndrome (LQTS) or sudden arrhythmic death syndrome (SADS). We examined the genetic variation of SLN in patients with the arrhythmic disorders AF, LQTS and SADS.
  
  
  METHODS
  We screened the coding region of SLN for mutations using single strand conformation polymorphism/heteroduplex analysis on PCR-amplified genomic DNA from 95 unrelated LQTS patients, 59 SADS cases and 147 patients with atrial fibrillation (AF) and 92 controls. Aberrant conformers were sequenced.
  
  
  RESULTS
  No mutations or polymorphisms were found in the coding sequence. A G>C transition in the highly conserved position +1 of the 3'untranslated region (3'UTR) was found in two SADS cases. A polymorphism, a G>C transition at position -65 in the 5'untranslated region (5'UTR), was found with a G allele frequency of 0.48. A borderline significant difference in genotype distribution of the latter polymorphism was found between the AF group and controls.
  
  
  CONCLUSIONS
  Mutations in the coding region of SLN are not frequently involved in LQTS, SADS or AF. Whether the described 3'- and 5'UTR variants have functional significance must await further studies.
authors.affiliation: Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Mia Titine
authors.initials: MT
authors.lastname: Nyberg
authors.forename: Birgitte
authors.initials: B
authors.lastname: Stoevring
authors.forename: Elijah Raphael
authors.initials: ER
authors.lastname: Behr
authors.forename: Lasse Steen
authors.initials: LS
authors.lastname: Ravn
authors.forename: William J
authors.initials: WJ
authors.lastname: McKenna
authors.forename: Michael
authors.initials: M
authors.lastname: Christiansen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001281:Atrial Fibrillation / Q000453:epidemiology / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D017124:Conserved Sequence; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D014644:Genetic Variation; D006801:Humans; D008133:Long QT Syndrome / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011510:Proteolipids / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013577:Syndrome
chemical_list: D009124:Muscle Proteins; D011510:Proteolipids; C077258:sarcolipin