Analysis of PAC1 receptor gene variants in Caucasian and African American infants dying of sudden infant death syndrome

Acta Paediatr. 2013 Dec;102(12):e546-52. doi: 10.1111/apa.12405.


Aim: Stress peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), has been implicated in sudden infant death syndrome (SIDS). The aim of this exploratory study was to determine whether variants in the gene encoding the PACAP-specific receptor, PAC1, are associated with SIDS in Caucasian and African American infants.

Methods: Polymerase chain reaction and Sanger DNA sequencing was used to compare variants in the 5'-untranslated region, exons and intron-exon boundaries of the PAC1 gene in 96 SIDS cases and 96 race- and gender-matched controls.

Results: The intron 3 variant, A/G: rs758995 (variant 'h'), and the intron 6 variant, C/T: rs10081254 (variant 'n'), were significantly associated with SIDS in Caucasians and African Americans, respectively (p < 0.05). Also associated with SIDS were interactions between the variants rs2302475 (variant 'i') in PAC1 and rs8192597 and rs2856966 in PACAP among Caucasians (p < 0.02) and rs2267734 (variant 'q') in PAC1 and rs1893154 in PACAP among African Americans (p < 0.01). However, none of these differences survived post hoc analysis.

Conclusion: Overall, this study does not support a strong association between variants in the PAC1 gene and SIDS; however, a number of potential associations between race-specific variants and SIDS were identified that warrant targeted investigations in future studies.

Keywords: Genetic variant; PAC1 receptor; Pituitary adenylate cyclase activating polypeptide; Sudden infant death syndrome.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Americans / genetics
  • Case-Control Studies
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Infant
  • Male
  • Maryland / epidemiology
  • Polymorphism, Single Nucleotide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / genetics*
  • Sudden Infant Death / ethnology
  • Sudden Infant Death / genetics*


  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I