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.
Department of Cardiology, Children's Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA. igor@enders.tch.harvard.edu
Igor
I
Splawski
Katherine W
KW
Timothy
Michihiro
M
Tateyama
Colleen E
CE
Clancy
Alka
A
Malhotra
Alan H
AH
Beggs
Francesco P
FP
Cappuccio
Giuseppe A
GA
Sagnella
Robert S
RS
Kass
Mark T
MT
Keating
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