Evidence for an association between infant mortality and homozygosity for the arctic variant of carnitine palmitoyltransferase 1A.
Evidence for an association between infant mortality and homozygosity for the arctic variant of carnitine palmitoyltransferase 1A.
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DOI：
10.1038/gim.2015.197
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发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Koeller DM
中科院分区：
文献类型：
--
作者：
Gessner BD;Wood T;Johnson MA;Richards CS;Koeller DM
阿拉斯加的婴儿死亡率最高的是来自阿拉斯加西部/北方的阿拉斯加原住民，这是一个肉毒碱棕榈酰转移酶1A（CPT 1A）遗传变异（c.1436 C>T;北极变异）流行率很高的人群。我们进行了一项不匹配的病例对照研究，以确定北极变异和婴儿死亡率之间的关系。病例是2006年至2010年的110名阿拉斯加土著婴儿死亡，对照是同期的395名阿拉斯加土著婴儿出生。除总体分析外，我们还进行了两项亚组分析，一项仅限于来自阿拉斯加西部/北方的受试者，另一项仅限于北极变异杂合子或纯合子婴儿。在阿拉斯加西部/北方居民中，66%的病例和61%的对照为纯合子（校正比值比[aOR] 2.5; 95%置信区间，1.3，5.0）。在纯合子或杂合子婴儿中，58%的病例和44%的对照为纯合子（aOR，2.3; 95%CI，1.3，4.0）。与感染相关的死亡更可能是纯合子（OR，2.9; 95%CI，1.0 - 8.0）。纯合子与肺炎、败血症或脑膜炎的发病前病史密切相关。北极变异的纯合性与婴儿死亡风险增加有关，这可能部分由传染病风险增加介导。还需要进一步的研究来确定我们报告的相关性是否代表CPT 1A北极变异与总体和传染病特异性死亡率之间的因果关系。
Infant mortality in Alaska is highest among Alaska Native people from Western/Northern Alaska, a population with a high prevalence of a genetic variant (c.1436C>T; The Arctic Variant) of carnitine palmitoyltransferase 1A (CPT1A). We performed an unmatched case-control study to determine the relationship between the arctic variant and infant mortality. Cases were 110 Alaska Native infant deaths from 2006 to 2010 and controls were 395 Alaska Native births from the same time period. In addition to the overall analysis we conducted two sub-analyses, one limited to subjects from Western/Northern Alaska, and one limited to infants heterozygous or homozygous for the arctic variant. Among Western/Northern Alaska residents, 66% of cases and 61% of controls were homozygous (adjusted odds ratio [aOR] 2.5; 95% confidence interval, 1.3, 5.0). Among homozygous or heterozygous infants, 58% of cases and 44% of controls were homozygous (aOR, 2.3; 95% CI, 1.3, 4.0). Deaths associated with infection were more likely to be homozygous (OR, 2.9; 95% CI, 1.0 to 8.0). Homozygosity was strongly associated with a pre-morbid history of pneumonia, sepsis, or meningitis. Homozygosity for the arctic variant is associated with increased risk of infant mortality, which may be mediated in part by an increase in infectious disease risk. Further studies will be needed to determine if the association we report represents a causal association between the CPT1A arctic variant and overall, and infectious disease specific mortality.