Tumor necrosis factor-α promoter variant 2 (TNF2) is associated with pre-term delivery, infant mortality, and malaria morbidity in western Kenya:: Asenibo Bay Cohort project IX
Tumor necrosis factor-α promoter variant 2 (TNF2) is associated with pre-term delivery, infant mortality, and malaria morbidity in western Kenya:: Asenibo Bay Cohort project IX
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DOI：
10.1002/gepi.1029
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发表时间：
2001-11-01
影响因子：
2.1
通讯作者：
Udhayakumar, V
中科院分区：
文献类型：
--
作者：
Aidoo, M;Mcelroy, PD;Udhayakumar, V
肿瘤坏死因子- α (tnf - α)基因启动子区域的多态性，在-308位置发生鸟嘌呤到腺嘌呤核苷酸的变化，TNF2与tnf - α产生增加有关。TNF2纯合子因脑型疟疾和其他传染病而患严重疾病和/或死亡的风险较高。我们调查了该等位基因对参与肯尼亚西部常年性恶性疟原虫传播强烈地区疟疾免疫流行病学队列研究的幼儿疟疾发病率和死亡率的影响。共有1048名儿童进行了基因分型。使用泊松回归和Cox比例风险模型来确定TNF-308变异与发病率和死亡率之间的关系。TNF1和TNF2等位基因频率分别为0.90和0.10。与TNF1纯合子相比，TNF2纯合子与早产相关[相对危险度（RR） 7.3, 95% CI, 2.85-18.9， P=0.002]和杂合子（RR 6.7, 95% CI 2.0-23.0， P=0.008）。在早产儿童中，与TNF1相比，TNF2等位基因与婴儿期死亡风险较高显著相关（RR 7.47, 95% CI 2.36-23.6）。TNF2纯合子的死亡风险高于杂合子。TNF2等位基因与高密度恶性疟原虫血症显著相关（RR 1.11, 95% CI 1.0-1.24）。在低出生体重儿童中，TNF2等位基因与严重贫血相关（RR 2.16, 95% CI 1.17-4.01），并显示出严重疟疾性贫血的风险趋势（RR 1.99, 95% CI 0.89-4.46）。这些数据表明，TNF2是该地区儿童早产和幼儿死亡以及疟疾发病率的一个危险因素。需要进一步了解这种关联背后的致病机制。麝猫。中华流行病学杂志，2001,21(2):591 - 591。(C) 2001 Wiley-Liss, Inc。
A polymorphism in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene, with a guanine to adenine nucleotide change at position -308, TNF2 is associated with increased TNF-alpha production. TNF2 homozygotes have a higher risk of severe disease and/or death due to cerebral malaria and other infectious diseases. We investigated the impact of this allele on malaria morbidity and mortality in young children who participated in an immuno-epidemiologic cohort study of malaria in an area of intense perennial Plasmodium falciparum transmission in western Kenya. A total of 1,048 children were genotyped. Poisson regression and Cox proportional hazards models were used to determine the relationship between TNF-308 variants and morbidity and mortality. The gene frequencies of the TNF1 and TNF2 alleles were 0.90 and 0.10, respectively. TNF2 homozygosity was associated with pre-term birth when compared with TNF1 homozygotes [relative risk (RR) 7.3, 95% CI, 2.85-18.9, P=0.002) and heterozygotes (RR 6.7, 95% CI 2.0-23.0, P=0.008). Among children born prematurely, the TNF2 allele was significantly associated with a higher risk of death in infancy compared with TNF1 (RR 7.47, 95% CI 2.36-23.6). The risk of death was higher among TNF2 homozygotes than among heterozygotes. The TNF2 allele was significantly associated with high density P falciparum parasitemia (RR 1.11, 95% CI 1.0-1.24). Among low birth weight children, the TNF2 allele was associated with severe anemia (RR 2.16, 95% CI 1.17-4.01) and showed a trend toward a risk for severe malaria anemia (RR 1.99, 95% CI 0.89-4.46). These data suggest that TNF2 is a risk factor for pre-term birth and early childhood mortality and malaria morbidity in children in this region. Further understanding of the pathogenic mechanisms underlying this association is required. Genet. Epidemiol. 21:201-211, 2001. (C) 2001 Wiley-Liss, Inc.