Research suggests mutations located in ten genetic loci may predispose individuals to sudden cardiac death

AFP (3/23) reported, "Scientists combing the human genome have discovered…common genetic mutations that boost the risk of sudden cardiac" death (SCD) and ventricular arrhythmias, according to two recently published studies published online Mar. 22 in the journal Nature. "Heart disease is the number one killer worldwide, claiming upward of 17 million lives every year," data collected by the World Health Organization reveal. It has been well documented that "smoking, obesity, and high cholesterol are common risk factors, but genes can be a critical factor too." So, "in the absence of symptoms, identifying genetic variants that affect the timing of heart contractions — known as the 'QT interval' — could become a critical means of predicting the likelihood of sudden cardiac death."

For the first study, one international team comprised of some 40 scientists, including investigators from Johns Hopkins University, decided to analyze "the genomes of 15,842 individuals whose QT intervals were measured," CBC News (3/23) added. The goal was matching "subtle changes in gene sequence with abnormal patterns of heart contraction." Eventually, "after screening 2.5 million genetic markers for variations that change the QT interval, they found alterations at 10 locations," Canada's Globe and Mail (3/23, Bielski) reported. Four of the variations came as a surprise, as the group "had no clue" they "were involved in cardiac biology at all," Hopkins' team member Dan Arking, PhD, pointed out.

In total, "14 gene variants," located "in 10 different gene regions," were implicated, HealthDay (3/23, Preidt) clarified. "A companion study in the same issue of Nature Genetics looked at more than 15,000 people and confirmed 12 of the 14 variants identified in the first study," while pinpointing "two additional gene regions." Study author Christopher Newton-Cheh, MD, of the Massachusetts General Hospital, commented, "We were very reassured to see such strong replication in two independent studies."

According to MedPage Today (3/23, Gever), both teams "confirmed that variants in the NOS1AP gene, encoding nitric oxide synthase adapter protein, were significantly associated with cardiac repolarization. In addition, the following genes were identified as helping to predict QT interval abnormalities: KCNQ1, a potassium channel gene; KCNH2, a potassium channel gene; KCNJ2, a potassium channel gene; SCN5A, a sodium channel gene; ATP1B1, maintains sodium and potassium gradients; PLN, regulates sarcoplasmic ATPase; LITAF, encodes a DNA-binding protein, CNOT1 region," and RNF207, which both have "functions [that are] uncertain." Dr. Newton-Cheh explained that "the 10 genes explained 5.4 percent of the variation in QT intervals in Framingham Heart Study participants and 6.5 percent among people in the Rotterdam study." Yet, the "genes were less predictive in the Cardiovascular Health Study, explaining 2.3 percent of QT interval variation."

Still, team member Gonçalo Abecasis, from the University of Michigan, "commented that these associations could be important in tailoring drug treatments," MedWire (3/23, Price) noted. "Changes in QT interval are common side effects of cardiac drugs, often leading to investigational drugs being dropped. Thus, these new risk loci could identify patients at particular risk for such complications with established drugs, as well as aiding development of drugs that avoid these complications in the first place."