Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery
Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery
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DOI：
10.1016/s0022-5223(03)01188-7
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发表时间：
2003-12-01
影响因子：
6
通讯作者：
Jarvik, GP
中科院分区：
文献类型：
--
作者：
Gaynor, JW;Gerdes, M;Jarvik, GP
背景：越来越多的人认识到先天性心脏病修复后的一些儿童的不良神经发育后遗症。即使在患有相同心脏缺陷的儿童中，发育结果也存在显著的个体间差异。载脂蛋白E基因多态性已被确定为中枢神经系统损伤后神经功能恢复不良的危险因素。方法：对年龄小于或等于6个月接受体外循环先天性心脏病修补术的患者进行单机构前瞻性研究，以评估载脂蛋白E基因型与术后神经发育功能障碍之间的关系。在1岁时使用Bayley婴儿发育量表评估发育结果：244例患者进行了一年的评估。校正术前和术后协变量后，包括胎龄、手术年龄、性别、种族、社会经济状况、心脏缺陷和深低温停循环的使用，载脂蛋白E ε 2等位基因与Bayley婴儿发育量表的精神发育指数评估的神经功能预后较差相关（P = 0.036）。载脂蛋白E ε 2等位基因的患者有大约7点的精神发育指数下降。结论：载脂蛋白E ε 2等位基因携带者在婴儿心脏手术后1年的精神发育指数评分显着降低。该效应与种族、社会经济地位、心脏缺陷和深低温停循环的使用无关。未检测到载脂蛋白E ε 4等位基因的影响。降低中枢神经系统损伤后神经弹性和损害神经元修复的遗传多态性是婴儿心脏手术后神经发育功能障碍的重要危险因素。
Background: There has been increasing recognition of adverse neurodevelopmental sequelae in some children after repair of congenital heart defects. Even among children with the same cardiac defect, significant interindividual variation exists in developmental outcome. Polymorphisms of apolipoprotein E have been identified as a risk factor for worse neurologic recovery after central nervous system injury.Methods: A single-institution prospective study of patients less than or equal to6 months of age undergoing cardiopulmonary bypass for repair of congenital heart defects was undertaken to evaluate the association between apolipoprotein E genotype and postoperative neurodevelopmental dysfunction. Developmental outcomes were evaluated at 1 year of age by using the Bayley Scales of Infant Development.Results: One-year evaluation was performed in 244 patients. After adjustment for preoperative and postoperative covariates-including gestational age, age at operation, sex, race, socioeconomic status, cardiac defect, and use of deep hypothermic circulatory arrest-the apolipoprotein E epsilon2 allele was associated with a worse neurologic outcome as assessed by the Psychomotor Developmental Index of the Bayley Scales of Infant Development (P =.036). Patients with the apolipoprotein E epsilon2 allele had approximately a 7-point decrease in the Psychomotor Developmental Index.Conclusions: Apolipoprotein E epsilon2 allele carriers had significantly lower Psychomotor Development Index scores at 1 year of age after infant cardiac surgery. The effect was independent of ethnicity, socioeconomic status, cardiac defect, and use of deep hypothermic circulatory arrest. An effect of the apolipoprotein E epsilon4 allele was not detected. Genetic polymorphisms that decrease neuroresiliency and impair neuronal repair after central nervous system injury are important risk factors for neurodevelopmental dysfunction after infant cardiac surgery.