Association of the serotonin transporter gene with sudden infant death syndrome: A haplotype analysis

Debra E. Weese-Mayer*, Lili Zhou, Elizabeth M. Berry-Kravis, Brion S. Maher, Jean M. Silvestri, Mary L. Marazita

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

102 Scopus citations


Serotonergic receptor binding in the arcuate nucleus, n. raphé obscurus, and other medullary regions is decreased in sudden infant death syndrome (SIDS) cases. Further, an insertion/deletion polymorphism in the promoter region of the serotonin transporter protein (5-HTT) gene has recently been associated with risk of SIDS. 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). To further elucidate the role of the 5-HTT gene in SIDS, we investigated the 5-HTT intron 2 polymorphism, which also differentially regulates 5-HTT expression with the 12 repeat allele being the more effective promoter. In a cohort of 90 SIDS cases (44 African-American and 46 Caucasian) and gender/ethnicity-matched controls, significant positive associations were found between SIDS and the intron 2 genotype distribution (P-value=0.041) among African-American SIDS vs. African-American controls, specifically with the 12/12 genotype (P-value = 0.03), and with the 12 repeat allele (P-value=0.018). The frequency of the 12/ 12 genotype and 12-repeat allele was significantly different (P<0.001) between the African-American and Caucasian SIDS cases. Furthermore, the promoter and intron 2 loci were in significant linkage disequilibrium, and the L-12 haplotype was significantly associated with SIDS in the African-American (P = 0.002) but not Caucasian (P = 0.117) subgroups. These results indicate a relationship between SIDS and the 12-repeat allele of the intron 2 variable number tandem repeat of the 5-HTT gene in African-Americans, and a significant role of the haplotype containing the 12-repeat allele and the promoter L-allele in defining SIDS risk in African-Americans. These data, if confirmed in larger studies, may begin to explain the differences in SIDS incidence by ethnicity, suggest a role for levels of 5-HTT expression in generation of SIDS susceptibility, and provide an important tool for identifying at-risk individuals and estimating the risk of recurrence.

Original languageEnglish (US)
Pages (from-to)238-245
Number of pages8
JournalAmerican Journal of Medical Genetics
Volume122 A
Issue number3
StatePublished - Oct 15 2003


  • 5-HTT
  • Intron 2
  • Serotonin transporter
  • Sudden infant death syndrome
  • hSERT

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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