Publication Date:
2002-08-24
Description:
Every year, approximately 450,000 individuals in the United States die suddenly of cardiac arrhythmia. We identified a variant of the cardiac sodium channel gene SCN5A that is associated with arrhythmia in African Americans (P = 0.000028) and linked with arrhythmia risk in an African-American family (P = 0.005). In transfected cells, the variant allele (Y1102) accelerated channel activation, increasing the likelihood of abnormal cardiac repolarization and arrhythmia. About 13.2% of African Americans carry the Y1102 allele. Because Y1102 has a subtle effect on risk, most carriers will never have an arrhythmia. However, Y1102 may be a useful molecular marker for the prediction of arrhythmia susceptibility in the context of additional acquired risk factors such as the use of certain medications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Splawski, Igor -- Timothy, Katherine W -- Tateyama, Michihiro -- Clancy, Colleen E -- Malhotra, Alka -- Beggs, Alan H -- Cappuccio, Francesco P -- Sagnella, Giuseppe A -- Kass, Robert S -- Keating, Mark T -- HL53773/HL/NHLBI NIH HHS/ -- P01 HL 67849/HL/NHLBI NIH HHS/ -- R01 HL 56810/HL/NHLBI NIH HHS/ -- R01 HL48074/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2002 Aug 23;297(5585):1333-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cardiology, Children's Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA. igor@enders.tch.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12193783" target="_blank"〉PubMed〈/a〉
Keywords:
Adolescent
;
Adult
;
African Continental Ancestry Group/*genetics
;
Aged
;
Alleles
;
Amino Acid Sequence
;
Arrhythmias, Cardiac/etiology/*genetics
;
Case-Control Studies
;
Cell Line
;
Child
;
Electrocardiography
;
Female
;
*Genetic Predisposition to Disease
;
*Genetic Variation
;
Humans
;
Ion Channel Gating
;
Long QT Syndrome/genetics
;
Male
;
Middle Aged
;
Molecular Sequence Data
;
NAV1.5 Voltage-Gated Sodium Channel
;
Patch-Clamp Techniques
;
Pedigree
;
*Point Mutation
;
Polymorphism, Single-Stranded Conformational
;
Probability
;
Risk Factors
;
Sodium Channels/chemistry/*genetics/metabolism
;
Syncope
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
