A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y

Leigh D. Plant, Peter N. Bowers, Qianyong Liu, Thomas Morgan, Tingting Zhang, Matthew W. State, Weidong Chen, Rick A Kittles, Steve A N Goldstein

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

Thousands die each year from sudden infant death syndrome (SIDS). Neither the cause nor basis for varied prevalence in different populations is understood. While 2 cases have been associated with mutations in type Vα, cardiac voltage-gated sodium channels (SCN5A), the "Back to Sleep" campaign has decreased SIDS prevalence, consistent with a role for environmental influences in disease pathogenesis. Here we studied SCN5A in African Americans. Three of 133 SIDS cases were homozygous for the variant S1103Y. Among controls, 120 of 1,056 were carriers of the heterozygous genotype, which was previously associated with increased risk for arrhythmia in adults. This suggests that infants with 2 copies of S1103Y have a 24-fold increased risk for SIDS. Variant Y1103 channels were found to operate normally under baseline conditions in vitro. As risk factors for SIDS include apnea and respiratory acidosis, Y1103 and wild-type channels were subjected to lowered intracellular pH. Only Y1103 channels gained abnormal function, demonstrating late reopenings suppressible by the drug mexiletine. The variant appeared to confer susceptibility to acidosis-induced arrhythmia, a gene-environment interaction. Overall, homozygous and rare heterozygous SCN5A missense variants were found in approximately 5% of cases. If our findings are replicated, prospective genetic testing of SIDS cases and screening with counseling for at-risk families warrant consideration.

Original languageEnglish (US)
Pages (from-to)430-435
Number of pages6
JournalJournal of Clinical Investigation
Volume116
Issue number2
DOIs
StatePublished - Feb 1 2006
Externally publishedYes

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Sudden Infant Death
Sodium Channels
African Americans
Cardiac Arrhythmias
Mexiletine
Voltage-Gated Sodium Channels
Respiratory Acidosis
Gene-Environment Interaction
Genetic Testing
Apnea
Acidosis
Counseling
Sleep
Genotype
Mutation
Pharmaceutical Preparations
Population

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Plant, L. D., Bowers, P. N., Liu, Q., Morgan, T., Zhang, T., State, M. W., ... Goldstein, S. A. N. (2006). A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y. Journal of Clinical Investigation, 116(2), 430-435. https://doi.org/10.1172/JCI25618

A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y. / Plant, Leigh D.; Bowers, Peter N.; Liu, Qianyong; Morgan, Thomas; Zhang, Tingting; State, Matthew W.; Chen, Weidong; Kittles, Rick A; Goldstein, Steve A N.

In: Journal of Clinical Investigation, Vol. 116, No. 2, 01.02.2006, p. 430-435.

Research output: Contribution to journalArticle

Plant, LD, Bowers, PN, Liu, Q, Morgan, T, Zhang, T, State, MW, Chen, W, Kittles, RA & Goldstein, SAN 2006, 'A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y', Journal of Clinical Investigation, vol. 116, no. 2, pp. 430-435. https://doi.org/10.1172/JCI25618
Plant, Leigh D. ; Bowers, Peter N. ; Liu, Qianyong ; Morgan, Thomas ; Zhang, Tingting ; State, Matthew W. ; Chen, Weidong ; Kittles, Rick A ; Goldstein, Steve A N. / A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y. In: Journal of Clinical Investigation. 2006 ; Vol. 116, No. 2. pp. 430-435.
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