Researchers find a genetic connection in Sudden Infant Death Syndrome

Researchers at Rush-Presbyterian-St. Luke’s Medical Center have found evidence supporting a relationship between SIDS and the 5-HTT gene in both African-Americans and Caucasians. They found a significant positive association between SIDS and the L/L genotype, and between SIDS and the 5-HTT L allele, and a negative association between SIDS and the S/S genotype. This information might eventually lead to the identification of infants at risk for SIDS.

Sudden Infant Death Syndrome (SIDS) claims the lives of more than 2,500 American infants every year, and African American children are far more likely to fall victim than Caucasians. Previous research into a genetic connection has pointed to a possible relationship between SIDS and a gene (5-HTT) that regulates serotonin uptake.

Dr. Debra E. Weese-Mayer, professor of pediatrics at Rush-Presbyterian-St. Luke’s Medical Center, led the new study. The study will appear in an upcoming print issue of the American Journal of Medical Genetics and will be published online January 17 via Wiley InterScience.

This study of SIDS and the 5-HTT gene was motivated by previous observations of decreased serotonergic receptor binding in SIDS cases. The 5-HTT gene regulates membrane uptake of serotonin and was therefore considered a likely candidate for SIDS studies. Furthermore, a recent Japanese study of the 5-HTT gene found an association between SIDS and the L/L genotype and L allele.

Seeking a similar association in an American population, researchers collected DNA samples from 87 U.S. SIDS cases, some Caucasian and some African-American. They also collected DNA from two sets of control subjects. The first set was screened for family history of SIDS or other relevant conditions, then matched to the SIDS cases for ethnicity and gender. The second set of controls included 334 random DNA samples used to determine population genotype frequencies. For each DNA sample, the 5-HTTLPR polymorphism was genotyped.

The results suggest an association between SIDS and the 5-HTT gene. “There was a significant difference in genotype distribution and an increased frequency of the L allele in SIDS cases versus ethnicity/gender matched controls with no family history of SIDS or autonomic dysfunction,” the authors report. “Furthermore, there were significantly fewer SIDS cases versus controls with no long allele (S/S genotype) in the entire cohort and within the Caucasian subgroup; and significantly more SIDS cases versus controls with no short allele (L/L genotype) in the entire cohort.”

The researchers also found that genotype frequency distributions and allele frequency distributions for 5-HTT were significantly different when evaluated across all ethnic groups. Despite ethnic variations, however, SIDS cases were more likely than controls to have the long allele in the Japanese, Caucasian, and African American study samples.

The study’s results are compelling, though limited by the research design that included only confirmed anonymous SIDS cases from the NIH-supported University of Maryland Brain Bank, according to Dr. Weese-Mayer. Further studies should encompass larger numbers and more ethnicities and also include the 5-HTT intron 2 VTNR which influences gene expression. Likewise, Dr. Weese-Mayer et al pointed out that “recognizing the strong relationship between tobacco exposure (prenatal and postnatal) and SIDS risk, future studies of genetic polymorphisms must also include detailed smoking history to clarify the role of gene-environment interaction.”

“If a larger data set reflects observations similar to those in this report,” the authors conclude, “the serotonergic system will represent a key area for further investigation into the causal basis for SIDS, with the goal of identifying genetic risk factors that will aide in recognizing at-risk individuals who require specialized intervention strategies and in counseling families as to the risk of recurrence.”