Sudden infant death syndrome (SIDS) in African Americans: polymorphisms in the gene encoding the stress peptide pituitary adenylate cyclase-activating polypeptide (PACAP).
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.
Cummings
Kevin J
KJ
Department of Physiology and Biophysics, Hotchkiss Brain Institute and Institute of Maternal and Child Health, University of Calgary, AB, Canada.
Klotz
Cherise
C
Liu
Wei-Qiao
WQ
Weese-Mayer
Debra E
DE
Marazita
Mary L
ML
Cooper
Margaret E
ME
Berry-Kravis
Elizabeth M
EM
Tobias
Rose
R
Goldie
Cameron
C
Bech-Hansen
N Torben
NT
Wilson
Richard Ja
RJ
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*
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide