Sudden infant death syndrome (SIDS) in African Americans: polymorphisms in the gene encoding the stress peptide pituitary adenylate cyclase‐activating polypeptide (PACAP)

Cummings, Kevin J.; Klotz, Cherise; Liu, Wei Qiao; Weese‐Mayer, Debra E.; Marazita, Mary L.; Cooper, Margaret E.; Berry‐Kravis, Elizabeth; Tobias, Rose; Goldie, Cameron; Bech-Hansen, N. Torben; Wilson, Richard J. A.

doi:10.1111/j.1651-2227.2008.01131.x

Cited by 33 publications

(25 citation statements)

References 56 publications

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“…The PACAP gene has been investigated in 46 Caucasian and 46 African-American SIDS, as well as in 92 living infant controls matched for ethnicity [78]. No associations between PACAP and SIDS were found in Caucasians, whereas in the African-American SIDS cases the G allele of rs2856966, leading to the substitution of aspartic acid with glycine, was significantly associated with SIDS.…”

Section: Brain Developmentmentioning

confidence: 98%

Gene variants predisposing to SIDS: current knowledge

Opdal

Rognum

2010

Forensic Sci Med Pathol

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Genetic risk factors play a role in sudden unexpected infant death; either as a cause of death, such as in cases with medium-chain acyl-coenzyme A dehydrogenase deficiency and cardiac arrest due to long QT syndrome, or as predisposing factors for sudden infant death syndrome (SIDS). Most likely genetic predisposition to SIDS represent a polygenic inheritance pattern leading to sudden death when combined with other risk factors, such as a vulnerable developmental stage of the central nervous system and/or the immune system, in addition to environmental risk factors, such as a common cold or prone sleeping position. Genes involved in the regulation of the immune system, cardiac function, the serotonergic network and brain function and development have so far emerged as the most important with respect to SIDS. The purpose of the present paper is to survey current knowledge on SIDS and possible genetic contributions.

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Section: Brain Developmentmentioning

confidence: 98%

Gene variants predisposing to SIDS: current knowledge

Opdal

Rognum

2010

Forensic Sci Med Pathol

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“…PAC1R −/− mice also exhibit a higher susceptibility to death during the neonatal period (Jamen et al ., ; Otto et al ., ). Moreover, mutations in the PACAP gene are possible risk factors in SIDS in a subset of African–American cases (Cummings et al ., ). These reports suggest that the PACAP −/− mouce is a good model for SIDS.…”

Section: Introductionmentioning

confidence: 97%

Impaired response to hypoxia in the respiratory center is a major cause of neonatal death of the PACAP‐knockout mouse

Arata

Nakamachi

Onimaru

et al. 2012

Eur J of Neuroscience

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Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide expressed widely in nervous tissues. PACAP-knockout ((-/-)) mice display a sudden infant death syndrome (SIDS)-like phenotype, although the underlying physiological mechanism to explain this remains unclear. Here, we report on the presence of abnormal respiratory activity in PACAP(-/-) mice under hypoxic conditions, which provides a basis for the SIDS-like phenotype. PACAP(-/-) mice display a lowered baseline respiratory activity compared with wild-type animals, and an abnormal response to hypoxia. More specifically, PACAP(-/-) mice at postnatal day 7 showed respiratory arrest in response to hypoxia. In contrast, their response to hypercapnic conditions was the same as that of wild-type mice. Histological and real-time PCR analyses indicated that the catecholaminergic system in the medulla oblongata was impaired in PACAP(-/-) mice, suggesting that endogenous PACAP affects respiratory centers in the medulla oblongata via its action on the catecholaminergic system. We propose that disruption of this system is involved in the SIDS-like phenotype of PACAP(-/-) mice. Thus, disorders of the catecholaminergic system involved with O(2) sensing could be implicated in underlying neuronal mechanisms responsible for SIDS.

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“…A protein that is associated with vasopressin signaling, named pituitary adenylate cyclase–activating polypeptide (PACAP; gene name ADCYAP1), results in a SIDS-like phenotype—characterized by a high increase in spontaneous neonatal death, exacerbated by hypothermia and hypoxia—when disrupted in mice (31). PACAP is widely expressed throughout the CNS, including autonomic control centers (32), and appears to be polymorphic in African American SIDS cases (6). Although it is not clear whether ADCYAP1 and HTR1A are expressed in the same cells, these proteins regulate opposing G protein–coupled receptor signaling pathways.…”

Section: Resultsmentioning

confidence: 99%

Systems-level perspective of sudden infant death syndrome

Salomonis

2014

Pediatr Res

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Sudden Infant Death Syndrome (SIDS) remains one of the primary causes of infant mortality in developed countries. While the causes of SIDS remain largely inconclusive, some of the most informative associations implicate molecular, genetic, anatomical, physiological and environmental (i.e., infant sleep) factors. Thus, a comprehensive and evolving systems-level model is required to understand SIDS susceptibility. Such models, by being powerful enough to uncover indirect associations, could be used to expand our list of candidate targets for in-depth analysis. We present an integrated WikiPathways model for SIDS susceptibility that includes associated cell systems, signaling pathways, genetics and animal phenotypes. Experimental and literature-based gene-regulatory data has been integrated into this model, to identify intersecting upstream control elements and associated interactions. To expand this pathway model, we performed a comprehensive analysis of existing proteomics data from brainstem samples of SIDS infants. From this analysis, we discovered changes in the expression of several proteins linked to known SIDS pathologies, including factors involved in glial cell production, hypoxia regulation, and synaptic vesicle release, in addition to interactions with annotated SIDS markers. Our results highlight new targets for further consideration that further enrich this pathway model, which, over time, can improve as a wiki-based, community curation project.

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Sudden infant death syndrome (SIDS) in African Americans: polymorphisms in the gene encoding the stress peptide pituitary adenylate cyclase‐activating polypeptide (PACAP)

Cited by 33 publications

References 56 publications

Gene variants predisposing to SIDS: current knowledge

Gene variants predisposing to SIDS: current knowledge

Impaired response to hypoxia in the respiratory center is a major cause of neonatal death of the PACAP‐knockout mouse

Systems-level perspective of sudden infant death syndrome

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