Role of SCN5A Y1102 polymorphism in sudden cardiac death in blacks

• Published in: Circulation (New York, N.Y.) N.Y.), 2005-08, Vol.112 (6), p.798-802
• Main Authors: BURKE, Alien, CREIGHTON, Wendy, MONT, Erik, LING LI, HOGAN, Susan, KUTYS, Robert, FOWLER, David, VIRMANI, Renu
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Africa - ethnology; Base Sequence; Biological and medical sciences; Black or African American; Black People - genetics; Blood and lymphatic vessels; Cardiology. Vascular system; Child; Coronary heart disease; Death, Sudden, Cardiac - epidemiology; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; DNA Primers; Exons; Female; Heart; Heart Arrest - genetics; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; Male; Medical sciences; Middle Aged; Muscle Proteins - genetics; NAV1.5 Voltage-Gated Sodium Channel; Polymorphism, Genetic; Sodium Channels - genetics; Tachycardia, Ventricular - genetics; United States
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.104.482760

The Y1102 polymorphism of the cardiac sodium channel (SCN5A) gene has been found in 13% of black Americans. It has been linked to lethal arrhythmias in black families with ventricular tachycardia. The prevalence of the Y1102 polymorphism in a series of sudden death in blacks is unknown. We investigated the incidence of the Y1102 polymorphism in a series of 289 sudden deaths in blacks by sequencing an amplified segment of DNA that contained the polymorphic site extracted from prospectively sampled frozen splenic tissue. The deaths were classified as noncardiac controls (n=107), cardiac arrhythmias with clear anatomic substrate (n=117), cardiac arrhythmias with no anatomic substrate except mild to moderate cardiac hypertrophy (n=40), and unexplained cardiac arrhythmias (n=25). Cause of death was determined after complete forensic autopsy and postmortem cardiac examination. The overall frequency of the Y1102 polymorphism was 9.0%. The frequency was 5.6% in noncardiac deaths, 4.3% in cardiac deaths with obvious anatomic substrate, 20.0% in arrhythmias with moderate hypertrophy, and 28% in unexplained arrhythmias. Adjusted for age and sex, the relative risk of an unexplained arrhythmic death was 8.4 (95% CI 2.1 to 28.6, P=0.001) with the Y1102 allele compared with noncardiac deaths. The relative risk for cardiac arrhythmias with mild cardiac hypertrophy was 4.9 (95% CI 1.3 to 13.4, P=0.01). The Y1102 allele is a risk factor in blacks for sudden cardiac death in the absence of obvious morphological findings or mild to moderate cardiomegaly.