Apolipoprotein E genotype predicts 24-month Bayley scales infant development score

被引:118
作者
Wright, RO
Hu, H
Silverman, EK
Tsaih, SW
Schwartz, J
Bellinger, D
Palazuelos, E
Weiss, ST
Hernandez-Avila, M
机构
[1] Childrens Hosp, Div Energy Med, Dept Pediat, Boston, MA 02115 USA
[2] Childrens Hosp, Div Energy Med, Dept Neurol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA
[4] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA
[5] Amer British Cowdray Hosp, Mexico City 18901, DF, Mexico
[6] Inst Nacl Perinatol, Inst Nacl Salud Publ, Mexico City 62508, DF, Mexico
[7] Natl Publ Hlth Inst, Ctr Invest Salud, Cuernavaca 62508, Morelos, Mexico
关键词
D O I
10.1203/01.PDR.0000090927.53818.DE
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
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 MDL. 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.
引用
收藏
页码:819 / 825
页数:7
相关论文
共 38 条
[1]  
Bailey J M, 2000, Novartis Found Symp, V233, P171, DOI 10.1002/0470870850.ch11
[2]   Neurobiology - Cholesterol - Making or breaking the synapse [J].
Barres, BA ;
Smith, SJ .
SCIENCE, 2001, 294 (5545) :1296-1297
[3]   The neurobiology of apolipoproteins and their receptors in the CNS and Alzheimer's disease [J].
Beffert, U ;
Danik, M ;
Krzywkowski, P ;
Ramassamy, C ;
Berrada, F ;
Poirier, J .
BRAIN RESEARCH REVIEWS, 1998, 27 (02) :119-142
[4]   LONGITUDINAL ANALYSES OF PRENATAL AND POSTNATAL LEAD-EXPOSURE AND EARLY COGNITIVE-DEVELOPMENT [J].
BELLINGER, D ;
LEVITON, A ;
WATERNAUX, C ;
NEEDLEMAN, H ;
RABINOWITZ, M .
NEW ENGLAND JOURNAL OF MEDICINE, 1987, 316 (17) :1037-1043
[5]   Alzheimer's disease: Neurodevelopment converges with neurodegeneration [J].
Bothwell, M ;
Giniger, E .
CELL, 2000, 102 (03) :271-273
[6]   A ROLE FOR APOLIPOPROTEIN-E, APOLIPOPROTEIN-A-I, AND LOW-DENSITY LIPOPROTEIN RECEPTORS IN CHOLESTEROL TRANSPORT DURING REGENERATION AND REMYELINATION OF THE RAT SCIATIC-NERVE [J].
BOYLES, JK ;
ZOELLNER, CD ;
ANDERSON, LJ ;
KOSIK, LM ;
PITAS, RE ;
WEISGRABER, KH ;
HUI, DY ;
MAHLEY, RW ;
GEBICKEHAERTER, PJ ;
IGNATIUS, MJ ;
SHOOTER, EM .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (03) :1015-1031
[7]   HLA, aging, and longevity:: A critical reappraisal [J].
Caruso, C ;
Candore, G ;
Romano, GC ;
Lio, D ;
Bonafè, M ;
Valensin, S ;
Franceschi, C .
HUMAN IMMUNOLOGY, 2000, 61 (09) :942-949
[8]   Lipoprotein receptors: Signaling functions in the brain? [J].
Cooper, JA ;
Howell, BW .
CELL, 1999, 97 (06) :671-674
[9]   Cholesterol metabolism in the brain [J].
Dietschy, JM ;
Turley, SD .
CURRENT OPINION IN LIPIDOLOGY, 2001, 12 (02) :105-112
[10]   Maternal bone lead as an independent risk factor for fetal neurotoxicity: A prospective study [J].
Gomaa, A ;
Hu, H ;
Bellinger, D ;
Schwartz, J ;
Tsaih, SW ;
Gonzalez-Cossio, T ;
Schnaas, L ;
Peterson, K ;
Aro, A ;
Hernandez-Avila, M .
PEDIATRICS, 2002, 110 (01) :110-118