Sudden infant death syndrome: Association with a promoter polymorphism of the serotonin transporter gene

Serotonergic receptor binding in the arcuate nucleus, n. raphé obscurus, and other medullary regions is decreased in sudden infant death syndrome (SIDS) cases. Further, a variable tandem repeat sequence polymorphism in the promoter region of the serotonin transporter protein ( 5‐HTT ) gene has recently been associated with risk of SIDS in a Japanese cohort. This polymorphism differentially regulates 5‐HTT expression, with the long allele (L), the SIDS‐associated allele, being a more effective promoter than the short allele (S). We therefore investigated the 5‐HTT promoter polymorphism in a cohort of 87 SIDS cases (43 African American and 44 Caucasian) and gender/ethnicity‐matched controls. Significant positive associations were found between SIDS and the 5‐HTT genotype distribution ( P  = 0.022), specifically with the L/L genotype ( P  = 0.048), and between SIDS and the 5‐HTT L allele ( P  = 0.005). There was also a significant negative association between SIDS and the S/S genotype ( P  = 0.011). The comparisons were repeated in the African American and Caucasian subgroups. The data patterns were consistent in the subgroups, i.e., the L/L genotype and L allele were increased in the cases, but not all subgroup comparisons were statistically significant. These results indicate a relationship between SIDS and the L allele of the 5‐HTT gene in African Americans and Caucasians, and if confirmed, will provide an important tool for identifying at‐risk individuals and estimating the risk of recurrence. © 2003 Wiley‐Liss, Inc.