Open Access Research article

SCN5A allelic expression imbalance in African-Americans heterozygous for the common variant p.Ser1103Tyr

Stacy AS Killen1, Jennifer Kunic2, Lily Wang3, Adele Lewis4, Bruce P Levy4, Michael J Ackerman5 and Alfred L George2*

Author Affiliations

1 Department of Pediatrics, Vanderbilt University, Nashville, TN, USA

2 Department of Medicine, Vanderbilt University, Nashville, TN, USA

3 Department of Biostatistics, Vanderbilt University, Nashville, TN, USA

4 Tennessee Medical Examiner's Office, Nashville, TN, USA

5 Department of Pediatrics, Mayo School of Medicine, Rochester, MN, USA

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BMC Medical Genetics 2010, 11:74  doi:10.1186/1471-2350-11-74

Published: 14 May 2010



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.


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.


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.


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.