Killen et al. BMC Medical Genetics 2010, 11:74 http://www.biomedcentral.com/1471-2350/11/74 Open Access RESEARCH ARTICLE BioMed Central © 2010 Killen et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Research article SCN5A allelic expression imbalance in African-Americans heterozygous for the common variant p.Ser1103Tyr Stacy AS Killen 1 , Jennifer Kunic 2 , Lily Wang 3 , Adele Lewis 4 , Bruce P Levy 4 , Michael J Ackerman 5 and Alfred L George Jr* 2 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 log 2 allelic expression ratios. However, there were no significant differences in the mean log 2 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. Background Every year in the United States more than 300,000 people die suddenly from an unexpected cardiac event [1], with coronary artery disease accounting for 80% of sudden cardiac death (SCD) in the adult population [2]. However, in children and adolescents, inherited arrhythmias, such as long-QT syndrome, Brugada syndrome, familial atrial fibrillation, catecholaminergic polymorphic ventricular tachycardia, and Wolff-Parkinson-White syndrome, are a leading cause of sudden death [2]. Sudden death from cardiac causes is more common in African-Americans than in Caucasians [3,4]. In adults, sudden death from nonatherosclerotic heart disease is more frequent in Afri- can-Americans, while during infancy, African-Americans are twice as likely as Caucasians to die from sudden infant death syndrome (SIDS) [5]. Mutations in SCN5A, the gene encoding the pore- forming α-subunit of the cardiac voltage-gated sodium channel, have been associated with sudden death in long QT syndrome and Brugada syndrome [6]. A common SCN5A genetic variant (p.Ser1103Tyr) that is found in 13% of African-Americans is associated with an increased risk for cardiac arrhythmia and sudden cardiac death in that population [7,8]. Further, the p.Ser1103Tyr variant is over-represented in African-American SIDS victims as compared to non-SIDS infant death cases [9,10] and sodium channels with the variant allele exhibit functional defects that may increase risk for life-threatening cardiac arrhythmias [7]. Because infants dying suddenly and unexpectedly are usually brought to autopsy, they provide a unique opportunity for studying tissue-specific expres- sion of a potentially lethal genetic variant. * Correspondence: al.george@vanderbilt.edu 2 Department of Medicine, Vanderbilt University, Nashville, TN, USA Full list of author information is available at the end of the article