Sudden infant death syndrome (SIDS) in African Americans: polymorphisms in the gene encoding the stress peptide pituitary adenylate cyclase-activating polypeptide (PACAP)
Sudden infant death syndrome (SIDS) in African Americans: polymorphisms in the gene encoding the stress peptide pituitary adenylate cyclase-activating polypeptide (PACAP)
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DOI：
10.1111/j.1651-2227.2008.01131.x
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发表时间：
2009-03-01
期刊：
影响因子：
3.8
通讯作者：
Wilson, Richard J. A.
中科院分区：
文献类型：
--
作者：
Cummings, Kevin J.;Klotz, Cherise;Wilson, Richard J. A.
目的：缺乏垂体腺苷酸环化酶激活多肽（PACAP）的小鼠在出生后第二周内容易猝死，呼吸和代谢紊乱使人联想到人类婴儿猝死综合征（SIDS）。在此，我们通过对92例SIDS患者和92例对照组的研究，验证了PACAP基因是与SIDS相关的遗传变异位点的假设。方法：采用聚合酶链反应和测序技术，我们检测了92例SIDS患者的PACAP基因（46名白人和46名非裔美国人）和92名种族和性别匹配的对照。我们发现在白种人中PACAP和SIDS之间没有显著的关联。然而，在非裔美国人中，PACAP外显子2内的非同义单核苷酸多态性（即天冬氨酸/甘氨酸编码变体，rs 2856966）与SIDS显著相关（p = 0.004），包含该多态性的单倍型也是如此（p < 0.0001）。甘氨酸是三倍，更有可能在这个位置在非洲裔美国人的小岛屿发展中国家的受害者（17例）比非洲裔美国人的控制（5例）。结论：这些数据是第一次提出之间的关联的PACAP基因和小岛屿发展中国家的编码区的变异。基于这些发现，进一步的调查是必要的功能的重要性，PACAP信号在新生儿的生存和作用的PACAP信号异常SIDS。
Aims: 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).Conclusion: 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.