SCN5Aallelic expression imbalance in African-Americans heterozygous for the common variant p.Ser1103Tyr

BMC Medical Genetics

Research Article

Lily Wang¹  Jennifer Kunic²  Alfred L George²  Michael J Ackerman³  Stacy AS Killen⁴  Bruce P Levy⁵  Adele Lewis⁵ 

[1] Department of Biostatistics, Vanderbilt University, Nashville, TN, USA;Department of Medicine, Vanderbilt University, Nashville, TN, USA;Department of Pediatrics, Mayo School of Medicine, Rochester, MN, USA;Department of Pediatrics, Vanderbilt University, Nashville, TN, USA;Tennessee Medical Examiner's Office, Nashville, TN, USA;

关键词: Sudden Cardiac Death;    Sudden Infant Death Syndrome;    Allelic Imbalance;    Brugada Syndrome;    Allelic Expression;   

DOI  :  10.1186/1471-2350-11-74

 received in 2009-10-26, accepted in 2010-05-14,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundHeterozygous 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.

【 授权许可】

Unknown   
© Killen et al; licensee BioMed Central Ltd. 2010. This article is published under license to 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.