Nelson Karin B, Dambrosia James M, Iovannisci David M, Cheng Suzanne, Grether Judith K, Lammer Edward
National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892-1447, and Children's Hospital and Research Center at Oakland, CA 94609-1673, USA.
Pediatr Res. 2005 Apr;57(4):494-9. doi: 10.1203/01.PDR.0000156477.00386.E7. Epub 2005 Feb 17.
In the present study, we examine whether selected genetic polymorphisms contribute to the development of cerebral palsy (CP) in very preterm infants. Subjects were 96 singleton infants with later-diagnosed CP and 119 control children, white non-Hispanic (n for CP=74, controls=88) or white Hispanic (CP=22, controls=31), born <32 wk gestation. Presence of CP was identified through state service agencies, with review of medical records. DNA extracted from archived neonatal blood was genotyped using multi-locus polymerase chain reaction amplification and immobilized sequence-specific oligonucleotide probes. Single nucleotide polymorphisms (SNPs) showing evidence of association with development of CP were endothelial nitric oxide synthase (eNOS) A(-922)G, factor 7 (F7) arg353gln and del(-323)10bp-ins, and lymphotoxin A (LTA) thr26asn. In white non-Hispanic children, beta-2 adrenergic receptor gln27glu was associated with CP risk; in Hispanic children, plasminogen activator inhibitor-1 (PAI-1) 4G(-675)5G and G11053T were associated with risk of CP. In a logistic regression considering these SNPs simultaneously in non-Hispanics, an association with CP was observed for heterozygotes of eNOS -922 (OR 3.0, CI 1.4-6.4), F7 (OR 2.7, CI 1.1-6.5), LTA (OR 2.1, CI 1.0-4.6), and PAI-1 (OR 3.2, CI 1.2-8.7). Factor 5, Factor 2, methylene tetrahydrofolate reductase, tumor necrosis factor-alpha, and other SNPs tested were not significantly associated with CP risk. We conclude that further study of genetic factors that may influence susceptibility to CP in very preterm infants is warranted.
在本研究中，我们调查了特定基因多态性是否会导致极早产儿患脑瘫（CP）。研究对象为96名单胎且后来被诊断为脑瘫的婴儿以及119名对照儿童，均为非西班牙裔白人（脑瘫组n = 74，对照组 = 88）或西班牙裔白人（脑瘫组 = 22，对照组 = 31），孕周均小于32周。通过州服务机构并查阅病历确定是否患有脑瘫。从存档的新生儿血液中提取DNA，使用多位点聚合酶链反应扩增和固定化序列特异性寡核苷酸探针进行基因分型。显示出与脑瘫发生相关证据的单核苷酸多态性（SNP）有内皮型一氧化氮合酶（eNOS）A(-922)G、凝血因子7（F7）arg353gln和del(-323)10bp-ins以及淋巴毒素A（LTA）thr26asn。在非西班牙裔白人儿童中，β-2肾上腺素能受体gln27glu与脑瘫风险相关；在西班牙裔儿童中，纤溶酶原激活物抑制剂-1（PAI-1）4G(-675)5G和G11053T与脑瘫风险相关。在对非西班牙裔人群同时考虑这些SNP的逻辑回归分析中，观察到eNOS -922杂合子（比值比3.0，置信区间1.4 - 6.4）、F7（比值比2.7，置信区间1.1 - 6.5）、LTA（比值比2.1，置信区间1.0 - 4.6）和PAI-1（比值比3.2，置信区间1.2 - 8.7）与脑瘫相关。凝血因子5、凝血因子2、亚甲基四氢叶酸还原酶、肿瘤坏死因子-α以及其他检测的SNP与脑瘫风险无显著关联。我们得出结论，有必要进一步研究可能影响极早产儿患脑瘫易感性的遗传因素。
