Oriá Reinaldo B, Patrick Peter D, Zhang Hong, Lorntz Breyette, de Castro Costa Carlos Maurício, Brito Gerly A C, Barrett Leah J, Lima Aldo A M, Guerrant Richard L
Center for Global Health, School of Medicine, Kluge's Children Rehabilitation Center, University of Virginia, Charlottesville, VA 22908, USA.
Pediatr Res. 2005 Feb;57(2):310-6. doi: 10.1203/01.PDR.0000148719.82468.CA. Epub 2004 Dec 20.
Polymorphisms in the apolipoprotein E (APOE) have constituted the major rationale to identify potential risk groups for developing late-onset Alzheimer's disease and help to predict recovery of cognitive function after brain injury. However, the APOE impact on cognitive development in children living in poor areas of the developing world, where we have discovered profound significant associations of early childhood diarrhea (at 0-2 y) with lasting impairments of growth, cognition, and school performance, is not known. Therefore, we conducted APOE genotyping in 72 Brazilian shantytown children under active surveillance since birth, using purified DNA extracted from buccal cell samples. We found a high frequency of APOE4 alleles (18% versus 9-11% expected) in children with lower diarrhea burdens. When we examined the children who experienced the heavier diarrhea burdens (greater than or equal to the median of seven illnesses in the first 2 y of life), those with APOE4 did significantly better in the coding subtest (p=0.01) when compared with APOE4-negative children with similar diarrhea burdens. Positive correlations between the APOE4 occurrence and coding scores remained, even after adjusting for family income, maternal education, and breast-feeding. Moreover, the APOE4-positive group, under heavy burdens of diarrhea, had preserved semantic fluency and the mean difference in fluency scores, p=0.025, a standardized coefficient for disproportional verbal fluency impairment. Our findings show that APOE4 is relatively common in favela children and suggest a protective role of the APOE4 allele in children with a history of heavy burdens of diarrhea in their first 2 y of life.
载脂蛋白E（APOE）基因多态性一直是识别晚发性阿尔茨海默病潜在风险群体的主要依据，并有助于预测脑损伤后认知功能的恢复情况。然而，在发展中世界贫困地区生活的儿童中，APOE对认知发育的影响尚不清楚。在这些地区，我们发现幼儿腹泻（0 - 2岁）与生长、认知和学业表现的长期损害之间存在着极为显著的关联。因此，我们对72名自出生起就接受主动监测的巴西贫民窟儿童进行了APOE基因分型，使用从口腔细胞样本中提取的纯化DNA。我们发现腹泻负担较轻的儿童中APOE4等位基因频率较高（18%，而预期为9 - 11%）。当我们检查腹泻负担较重的儿童（在生命的前2年中患病次数大于或等于7次的中位数）时，与腹泻负担相似的APOE4阴性儿童相比，携带APOE4的儿童在编码子测试中表现明显更好（p = 0.01）。即使在调整了家庭收入、母亲教育程度和母乳喂养等因素后，APOE4的出现与编码分数之间仍存在正相关。此外，在腹泻负担较重的情况下，APOE4阳性组保持了语义流畅性，流畅性分数的平均差异为p = 0.025，这是不成比例的语言流畅性损害的标准化系数。我们的研究结果表明，APOE4在贫民窟儿童中相对常见，并表明APOE4等位基因对生命最初2年有严重腹泻病史的儿童具有保护作用。
