Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The Robinson Institute, Australia.
Pediatrics. 2012 Feb;129(2):e414-23. doi: 10.1542/peds.2011-0739. Epub 2012 Jan 30.
Previous studies have suggested associations between certain genetic variants and susceptibility to cerebral palsy (CP). This study was designed to assess established and novel maternal and child genetic and epidemiologic risk factors for CP along with their interactions.
DNA from 587 case and 1154 control mother-child pairs was analyzed. A panel of 35 candidate single nucleotide polymorphisms (SNPs) were examined and included SNPs in genes associated with (1) thrombophilia, (2) inflammation, and (3) risk factors for CP (eg, preterm birth). Comparisons were specified a priori and made by using a χ(2) test.
There were 40 fetal and 28 maternal associations with CP when analyzed by CP subtype, gestational age, genotypes of apolipoprotein E, and haplotypes of mannose-binding-lectin. After Bonferroni correction for multiple testing, no fetal or maternal candidate SNP was associated with CP or its subtypes. Only fetal carriage of prothrombin gene mutation remained marginally associated with hemiplegia in term infants born to mothers with a reported infection during pregnancy. Odds ratio directions of fetal SNP associations were compared with previously reported studies and confirmed no trend toward association.
Except for the prothrombin gene mutation, individual maternal and fetal SNPs in our candidate panel were not found to be associated with CP outcome. Past reported SNP associations with CP were not confirmed, possibly reflecting type I error from small numbers and multiple testing in the original reports.
先前的研究表明，某些遗传变异与脑瘫（CP）的易感性之间存在关联。本研究旨在评估已建立和新的母婴遗传和流行病学危险因素，以及它们的相互作用。
对 587 例病例和 1154 例对照母婴对子的 DNA 进行了分析。研究人员检测了一组 35 个候选单核苷酸多态性（SNP），包括与（1）血栓形成倾向、（2）炎症和（3）CP 危险因素（如早产）相关的基因中的 SNP。比较是根据预先指定的标准，并使用 χ(2)检验进行。
当按 CP 亚型、胎龄、载脂蛋白 E 基因型和甘露聚糖结合凝集素单倍型分析时，有 40 个胎儿和 28 个母体与 CP 相关。经过多次检验的 Bonferroni 校正后，没有胎儿或母体候选 SNP 与 CP 或其亚型相关。只有在母亲在怀孕期间报告有感染的情况下，足月出生的婴儿携带凝血酶原基因突变，与偏瘫仍有轻微关联。与先前报道的研究相比，胎儿 SNP 关联的比值比方向得到了确认，没有关联的趋势。
除了凝血酶原基因突变外，我们候选基因座中的个体母婴 SNP 与 CP 结局无关。过去报道的与 CP 相关的 SNP 关联未得到证实，可能反映了原始报告中数量较少和多次检验的 I 型错误。
