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.
Conclusion: 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.