Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia.
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.
Splawski
Igor
I
Department of Cardiology, Children's Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA. igor@enders.tch.harvard.edu
Timothy
Katherine W
KW
Tateyama
Michihiro
M
Clancy
Colleen E
CE
Malhotra
Alka
A
Beggs
Alan H
AH
Cappuccio
Francesco P
FP
Sagnella
Giuseppe A
GA
Kass
Robert S
RS
Keating
Mark T
MT
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000595:Amino Acid Sequence; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D002460:Cell Line; D002648:Child; D004562:Electrocardiography; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D015640:Ion Channel Gating; D008133:Long QT Syndrome / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques; D010375:Pedigree; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011336:Probability; D012307:Risk Factors; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013575:Syncope; D014162:Transfection; D001741:Black or African American
D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels