Fohner Alison E, Garrison Nanibaa' A, Austin Melissa A, Burke Wylie
Department of Genetics, School of Medicine, Stanford University, Stanford, California, USA.
Treuman Katz Center for Pediatric Bioethics, Seattle Children's Research Institute, Seattle, Washington, USA.
Genet Med. 2017 Aug;19(8):851-857. doi: 10.1038/gim.2016.202. Epub 2017 Jan 26.
Carnitine palmitoyltransferase 1 isoform A (CPT1A) is a crucial enzyme for the transport of long-chain fatty acids into the mitochondria. The CPT1A p.P479L variant is found in high frequencies among indigenous populations residing on the west and north coasts of Alaska and Canada and in northeast Siberia and Greenland. Epidemiological studies have reported a statistical association between P479L homozygosity and infant death in Alaska Native and Canadian Inuit populations. Here, we review the available evidence about the P479L variant and apply to these data the epidemiological criteria for assessing causal associations. We found insufficient evidence to support a causal association with infant death and, further, that if a causal association is present, then the genotype is likely to be only one of a complex set of factors contributing to an increased risk of infant death. We conclude that additional research is needed to clarify the observed association and to inform effective preventative measures for infant death. In light of these findings, we discuss the policy implications for public health efforts because policies based on the observed association between P479L homozygosity and infant death data are premature.Genet Med advance online publication 26 January 2017.
肉碱棕榈酰转移酶1同工型A（CPT1A）是长链脂肪酸转运至线粒体过程中的关键酶。CPT1A p.P479L变异在居住于阿拉斯加和加拿大西海岸、西伯利亚东北部以及格陵兰岛的原住民中高频出现。流行病学研究报告称，在阿拉斯加原住民和加拿大因纽特人群中，P479L纯合性与婴儿死亡之间存在统计学关联。在此，我们回顾了关于P479L变异的现有证据，并将评估因果关联的流行病学标准应用于这些数据。我们发现支持与婴儿死亡存在因果关联的证据不足，而且，如果存在因果关联，那么该基因型可能只是导致婴儿死亡风险增加的复杂因素之一。我们得出结论，需要进一步研究以阐明所观察到的关联，并为预防婴儿死亡的有效措施提供依据。鉴于这些发现，我们讨论了对公共卫生工作的政策影响，因为基于所观察到的P479L纯合性与婴儿死亡数据之间的关联制定政策为时过早。《遗传医学》于2017年1月26日在线优先发表。
