Genetic polymorphisms and cerebral palsy in very preterm infants.
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.
Nelson
Karin B
KB
National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892-1447, and Children's Hospital and Research Center at Oakland, CA 94609-1673, USA. knelson@helix.nih.gov
Dambrosia
James M
JM
Iovannisci
David M
DM
Cheng
Suzanne
S
Grether
Judith K
JK
Lammer
Edward
E
D016022:Case-Control Studies; D002547:Cerebral Palsy / Q000175:diagnosis / Q000235:genetics*; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics; D005260:Female; D005838:Genotype; D005865:Gestational Age; D006801:Humans; D006973:Hypertension / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D009569:Nitric Oxide / Q000235:genetics; D011110:Polymorphism, Genetic; D011247:Pregnancy; D013927:Thrombosis / Q000235:genetics
D016207:Cytokines; D009569:Nitric Oxide