title: SCN5A allelic expression imbalance in African-Americans heterozygous for the common variant p.Ser1103Tyr.
abstract: BACKGROUND
  Heterozygous and homozygous carriers of SCN5A-p.Ser1103Tyr, a common genetic variant with functional effects among African-Americans, have an increased risk of sudden death. We hypothesized that some heterozygous carriers may have unequal expression of wild-type and variant alleles and secondarily that predominance of the variant gene copy could further increase risk for sudden death in this population.
  
  
  METHODS
  We quantified allele-specific expression of SCN5A-p.Ser1103Tyr by real-time reverse-transcription polymerase chain reaction (RT-PCR) in heart tissue from heterozygous African-American infants, who died from sudden infant death syndrome (SIDS) or from other causes, to test for allelic expression imbalance.
  
  
  RESULTS
  We observed significant allelic expression imbalance in 13 of 26 (50%) African-American infant hearts heterozygous for SCN5A-p.Ser1103Tyr, and a significant (p < 0.0001) bimodal distribution of log2 allelic expression ratios. However, there were no significant differences in the mean log2 allelic expression ratios in hearts of infants dying from SIDS as compared to infants dying from other causes and no significant difference in the proportion of cases with greater expression of the variant allele.
  
  
  CONCLUSIONS
  Our data provide evidence that SCN5A allelic expression imbalance occurs in African-Americans heterozygous for p.Ser1103Tyr, but this phenomenon alone does not appear to be a marker for risk of SIDS.
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Stacy A S
authors.initials: SA
authors.lastname: Killen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kunic
authors.forename: Lily
authors.initials: L
authors.lastname: Wang
authors.forename: Adele
authors.initials: A
authors.lastname: Lewis
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Levy
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ackerman
authors.forename: Alfred L
authors.initials: AL
authors.lastname: George
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D022981:Allelic Imbalance; D003645:Death, Sudden; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007223:Infant; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013398:Sudden Infant Death / Q000453:epidemiology / Q000235:genetics*
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