Wright Robert O, Hu Howard, Silverman Edwin K, Tsaih Shirng W, Schwartz Joel, Bellinger David, Palazuelos Eduardo, Weiss Scott T, Hernandez-Avila Mauricio
Department of Pediatrics, Children's Hospital, Boston, Massachusett 02115, USA.
Pediatr Res. 2003 Dec;54(6):819-25. doi: 10.1203/01.PDR.0000090927.53818.DE. Epub 2003 Aug 20.
Apolipoprotein E (APOE) regulates cholesterol and fatty acid metabolism, and may mediate synaptogenesis during neurodevelopment. To our knowledge, the effects of APOE4 isoforms on infant development have not been studied. This study was nested within a cohort of mother-infant pairs living in and around Mexico City. A multiple linear regression model was constructed using the 24-mo Mental Development Index (MDI) of the Bayley Scale as the primary outcome and infant APOE genotype as the primary risk factor of interest. Regression models stratified on APOE genotype were constructed to explore effect modification. Of 311 subjects, 53 (17%) carried at least one copy of the APOE4 allele. Mean (SD) MDI scores among carriers with at least one copy of APOE4 were 94.1 (14.3) and among E3/E2 carriers were 91.2 (14.0). After adjustment for covariates, APOE4 carrier status was associated with a 4.4 point (95% confidence interval: 0.1-8.7; p = 0.04) higher 24-mo MDI. In the stratified regression models, the negative effects for umbilical cord blood lead level on 24-mo MDI score was approximately 4-fold greater among APOE3/APOE2 carriers than among APOE4 carriers. These results suggest that subjects with the E4 isoform of APOE may have advantages over those with the E2 or E3 isoforms with respect to early life neuronal/brain development.
载脂蛋白E(APOE)调节胆固醇和脂肪酸代谢,并可能在神经发育过程中介导突触形成。据我们所知,APOE4亚型对婴儿发育的影响尚未得到研究。本研究嵌套于居住在墨西哥城及其周边地区的母婴队列中。构建了一个多元线性回归模型,以贝利量表的24个月心理发展指数(MDI)作为主要结局,婴儿APOE基因型作为主要感兴趣的危险因素。构建按APOE基因型分层的回归模型以探索效应修正。在311名受试者中,53名(17%)携带至少一份APOE4等位基因拷贝。携带至少一份APOE4拷贝的携带者的平均(标准差)MDI评分为94.1(14.3),E3/E2携带者的平均(标准差)MDI评分为91.2(14.0)。在对协变量进行调整后,APOE4携带者状态与24个月时MDI高4.4分(95%置信区间:0.1 - 8.7;p = 0.04)相关。在分层回归模型中,脐带血铅水平对24个月时MDI评分的负面影响在APOE3/APOE2携带者中比在APOE4携带者中大约大四倍。这些结果表明,就早期生命中的神经元/大脑发育而言,携带APOE E4亚型的受试者可能比携带E2或E3亚型的受试者具有优势。