Common genetic variation increases SIDS risk in African Americans

About five percent of deaths from SIDS (sudden infant death syndrome) in African Americans can be traced to defects in one gene and half of those deaths result from a common genetic variation that increases an infant's risk of developing an abnormal heart rhythm during times of environmental stress, a research team based at the University of Chicago reports in the February 2006 issue of the Journal of Clinical Investigation.

Children with two copies of the common genetic variation have a 24-fold increased risk of sudden death as infants. One out of nine African Americans carries one copy of the common variant. One copy does not appear to increase risk for infants.

"The common polymorphism alone does not cause SIDS," said Steven Goldstein, M.D., Ph.D., professor and chairman of pediatrics at the University of Chicago and director of the study. "Our findings suggest, however, that it renders infants vulnerable to environmental challenges - such as a long pause in respiration - that are tolerated by children without the mutation."

"The hope," he added, "is that findings like this may one day allow us to intervene. We might screen to identify children at high risk and teach parents how to lessen the likelihood of secondary challenges. We have already begun to evaluate drugs that may mitigate the risk."

SIDS - the sudden and unanticipated death of an infant with no detectable lethal disorder - is the leading cause of infant deaths in the United States, representing nearly one-third of deaths between one month and one year of age. African Americans have three times greater risk of SIDS than Caucasians and six times the risk of Hispanics or Asians, suggesting an important role for genetics.

The researchers studied the genes in tissue collected from 133 African-American infants with a diagnosis of SIDS after autopsy. They compared results with tissue samples from 1,056 African-American adults with no known health problems.

Their search focused on abnormalities in a gene called SCN5A, which has been associated with abnormal heart rhythms. Overall, the team found common and rare changes in this gene in five percent of SIDS deaths in African Americans. One specific variation, known as Y1103, was known to confer an eight-fold risk of cardiac arrhythmia in African-American adults with one copy.

In this study, the researchers found that having two copies of Y1103 was more common in infants who died from SIDS than in controls. Three out of the 133 African-American SIDS cases (2.3%) had two copies of Y1103, compared to only one individual out of 1,056 controls (0.1%). Four other SIDS cases had other damaging mutations in one copy of the gene.

How, they asked, might this variation contribute to SIDS?

The SCN5A gene codes for a sodium channel, a pore found in cardiac muscle cells that controls the passage of sodium ions in and out of the cell.