TY - JOUR
T1 - Overrepresentation of the proarrhythmic, sudden death predisposing sodium channel polymorphism S1103Y in a population-based cohort of African-American sudden infant death syndrome
AU - Van Norstrand, David W.
AU - Tester, David J.
AU - Ackerman, Michael J.
N1 - Funding Information:
DNA was extracted from autopsy blood using the Puregene DNA Isolation kit (Gentra, Minneapolis, MN, USA) or from frozen necropsy tissue using the Qiagen DNeasy Tissue Kit (Qiagen, Inc., Valencia, CA, USA). Genomic DNA derived from 100 healthy African-American subjects was obtained from the Human Genetic Cell Repository sponsored by the National Institute of General Medical Sciences and the Coriell Institute for Medical Research (Camden, NJ, USA) and served as ethnic-matched controls.
PY - 2008/5
Y1 - 2008/5
N2 - Background: The S1103Y-SCN5A polymorphism has been implicated as a proarrhythmic, sudden death predisposing risk factor in African Americans, including one postmortem investigation of African-American infants with sudden infant death syndrome (SIDS). Objective: The purpose of this study was to assess whether the relatively African-American-specific common polymorphism S1103Y in the SCN5A-encoded cardiac sodium channel is overrepresented in SIDS among African Americans. Methods: Seventy-one cases from a population-based cohort of unexplained infant deaths among African Americans (37 females and 34 males, average age 3 ± 2 months, age range birth to 11 months) were submitted to the Mayo Clinic Windland Smith Rice Sudden Death Genomics Laboratory for postmortem genetic testing. Polymerase chain reaction and a restriction digest assay were performed to genotype this cohort for S1103Y. Results: Targeted mutational analysis of exon 18 in SCN5A of the African-American SIDS cohort (n = 71) revealed the S1103Y polymorphism in 16 (22.5%) of 71 African-American cases of SIDS compared to 135 (11.6%) of 1,161 ostensibly healthy adult African Americans (P = .01). Conclusion: This study provides an independent assessment of the prevalence of S1103Y-SCN5A among African-American infants with sudden, unexpected, unexplained death prior to their first birthday. Further scrutiny and quantification of the risk apparently associated with S1103Y appear warranted.
AB - Background: The S1103Y-SCN5A polymorphism has been implicated as a proarrhythmic, sudden death predisposing risk factor in African Americans, including one postmortem investigation of African-American infants with sudden infant death syndrome (SIDS). Objective: The purpose of this study was to assess whether the relatively African-American-specific common polymorphism S1103Y in the SCN5A-encoded cardiac sodium channel is overrepresented in SIDS among African Americans. Methods: Seventy-one cases from a population-based cohort of unexplained infant deaths among African Americans (37 females and 34 males, average age 3 ± 2 months, age range birth to 11 months) were submitted to the Mayo Clinic Windland Smith Rice Sudden Death Genomics Laboratory for postmortem genetic testing. Polymerase chain reaction and a restriction digest assay were performed to genotype this cohort for S1103Y. Results: Targeted mutational analysis of exon 18 in SCN5A of the African-American SIDS cohort (n = 71) revealed the S1103Y polymorphism in 16 (22.5%) of 71 African-American cases of SIDS compared to 135 (11.6%) of 1,161 ostensibly healthy adult African Americans (P = .01). Conclusion: This study provides an independent assessment of the prevalence of S1103Y-SCN5A among African-American infants with sudden, unexpected, unexplained death prior to their first birthday. Further scrutiny and quantification of the risk apparently associated with S1103Y appear warranted.
KW - Arrhythmia
KW - Cardiac sodium channel gene SCN5A
KW - Long QT syndrome
KW - Sudden death
KW - Sudden infant death syndrome
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U2 - 10.1016/j.hrthm.2008.02.012
DO - 10.1016/j.hrthm.2008.02.012
M3 - Article
C2 - 18452875
AN - SCOPUS:42649091103
SN - 1547-5271
VL - 5
SP - 712
EP - 715
JO - Heart rhythm
JF - Heart rhythm
IS - 5
ER -