title: Sudden infant death syndrome (SIDS) in African Americans: polymorphisms in the gene encoding the stress peptide pituitary adenylate cyclase-activating polypeptide (PACAP).
abstract: OBJECTIVE
  Mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP) are prone to sudden death in the second post-natal week, having respiratory and metabolic disturbances reminiscent of the human Sudden Infant Death Syndrome (SIDS). Here we test the hypothesis that the human PACAP gene is a site of genetic variance associated with SIDS in a cohort of 92 victims and 92 matched controls.
  
  
  METHODS
  Using polymerase chain reaction and sequencing, we examined the PACAP gene in 92 SIDS cases (46 Caucasians and 46 African Americans) and 92 race- and gender-matched controls.
  
  
  RESULTS
  We found no significant associations between PACAP and SIDS in Caucasians. However, in the African Americans, a non-synonymous single nucleotide polymorphism (i.e. an aspartic acid/glycine coding variant, rs2856966) within exon 2 of PACAP was significantly associated with SIDS (p = 0.004), as were haplotypes containing this polymorphism (p < 0.0001). Glycine was three times more likely at this location in the African-American SIDS victims (17 cases) than African-American controls (5 cases).
  
  
  CONCLUSIONS
  These data are the first to suggest an association between a variant within the coding region of the PACAP gene and SIDS. Based on these findings, further investigations are warranted into the functional importance of PACAP signaling in neonatal survival and the role of PACAP-signaling abnormalities in SIDS.
authors.affiliation: Department of Physiology and Biophysics, Hotchkiss Brain Institute and Institute of Maternal and Child Health, University of Calgary, AB, Canada.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Cummings
authors.forename: Cherise
authors.initials: C
authors.lastname: Klotz
authors.forename: Wei-Qiao
authors.initials: WQ
authors.lastname: Liu
authors.forename: Debra E
authors.initials: DE
authors.lastname: Weese-Mayer
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Cooper
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Berry-Kravis
authors.forename: Rose
authors.initials: R
authors.lastname: Tobias
authors.forename: Cameron
authors.initials: C
authors.lastname: Goldie
authors.forename: N Torben
authors.initials: NT
authors.lastname: Bech-Hansen
authors.forename: Richard Ja
authors.initials: RJ
authors.lastname: Wilson
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D008297:Male; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics*; D011110:Polymorphism, Genetic; D013398:Sudden Infant Death / Q000208:ethnology / Q000235:genetics*
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide