Candidate Genes and Cerebral Palsy: A Population-Based Study
Candidate Genes and Cerebral Palsy: A Population-Based Study
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DOI：
10.1542/peds.2007-3758
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发表时间：
2008-11-01
期刊：
影响因子：
8
通讯作者：
Nelson, Karin B.
中科院分区：
文献类型：
--
作者：
Gibson, Catherine S.;MacLennan, Alastair H.;Nelson, Karin B.
OBJECTIVE.本研究的目的是检查是否选定的遗传多态性在婴儿与后来诊断的脑瘫。一项基于人群的病例对照研究进行了28个单核苷酸多态性测定新生儿筛查血斑。1986-1999年，在南澳，共有413名后来被诊断为脑瘫的儿童出生于白色妇女，对照组有856名儿童。基因型频率的分布在全脑性瘫痪，胎龄组，脑性瘫痪的类型和性别进行了检查。通过使用TaqMan分析进行基因分型。对于诱导型一氧化氮合酶，T等位基因在所有脑瘫儿童和足月出生的杂合子中更为常见。对于α-光氧还蛋白，纯合子变异状态与脑性瘫痪和痉挛性偏瘫或四肢瘫痪脑性瘫痪的风险相关。在足月儿中，内皮蛋白C受体单核苷酸多态性的杂合性在脑瘫儿童中更常见。在早产儿中，白细胞介素8的变异A等位基因和β 2肾上腺素能受体的杂合性与脑瘫风险相关。白细胞介素8杂合子状态与痉挛性双瘫相关。几个基因的变异与女孩的脑瘫有关，但与男孩无关。28个单核苷酸多态性中的两个与所有类型的痉挛性脑瘫在两个胎龄组和其他与脑瘫在胎龄或脑瘫亚组。其中一些关联支持了以前的研究结果。可能有遗传因素对脑瘫风险的贡献，并且需要对脑瘫中的基因和基因-环境相互作用进行进一步的研究。儿科2008; 122：1079-1085
OBJECTIVE. The objective of this study was to examine whether selected genetic polymorphisms in the infant are associated with later-diagnosed cerebral palsy.METHODS. A population-based case-control study was conducted of 28 single-nucleotide polymorphisms measured in newborn screening blood spots. A total of 413 children with later-diagnosed cerebral palsy were born to white women in South Australia in 1986-1999, and there were 856 control children. Distributions of genotypic frequencies were examined in total cerebral palsy, in gestational age groups, and by types of cerebral palsy and gender. Genotyping was performed by using a TaqMan assay.RESULTS. For inducible nitric-oxide synthase, possession of the T allele was more common in all children with cerebral palsy and for heterozygotes who were born at term. For lymphotoxin alpha, homozygous variant status was associated with risk for cerebral palsy and with spastic hemiplegic or quadriplegic cerebral palsy. Among term infants, heterozygosity for the endothelial protein C receptor single-nucleotide polymorphism was more frequent in children with cerebral palsy. In preterm infants, the variant A allele of interleukin 8 and heterozygosity for the beta-2 adrenergic receptor were associated with cerebral palsy risk. Interleukin 8 heterozygote status was associated with spastic diplegia. Variants of several genes were associated with cerebral palsy in girls but not in boys.CONCLUSIONS. Two of the 28 single-nucleotide polymorphisms examined were associated with all types of spastic cerebral palsy in both gestational age groups and others with cerebral palsy in gestational age or cerebral palsy subgroups. Some of these associations support previous findings. There may be a genetic contribution to cerebral palsy risk, and additional investigation is warranted of genes and gene-environment interactions in cerebral palsy. Pediatrics 2008; 122: 1079-1085