ObjectiveTo investigate associations between inherited cytokine polymorphisms and cerebral palsy in a large population-based case-control study.Study designGenomic DNA from the newborn screening cards of 443 Caucasian CP cases and 883 Caucasian controls was tested for five cytokine polymorphisms: Tumour Necrosis Factor alpha –308 (TNF-alpha-308), Mannose Binding Lectin –221 (MBL –221), and three polymorphisms in Exon 1 of the Mannose Binding Lectin gene at codons 52, 54 and 57.ResultsAt all gestational ages MBL codon 52 (homozygous or heterozygous) was associated with an increased risk of developing quadriplegia (OR 2.74, 0.95-6.96), and MBL codon 54 (homozygous or heterozygous) increased the risk of developing diplegia (OR 1.55, 1.03-2.32). For babies born at term, the risk of developing quadriplegia was associated with heterozygous TNF-alpha (OR 1.82, 1.04-3.15), and MBL codon 52 (homozygous or heterozygous OR 3.24, 0.91-9.42). MBL codon 54 (homozygous or heterozygous) was associated with diplegia (OR 2.12, 1.10-4.05). The presence of any polymorphism in MBL exon 1 at term approximately doubled the risk of developing diplegia (OR 1.94, 1.05-3.62). Carriage of an abnormal TNF-alpha allele was associated with hemiplegia for babies born <32 weeks gestation (OR 2.38, 1.02-5.58). Overall, the presence of any cytokine polymorphism was associated with CP (OR 1.37, 95% CI 1.02-1.84).ConclusionThe data derived from this large population sample of Caucasian cerebral palsy cases and controls demonstrate that carriage of polymorphisms in the TNF-alpha and MBL genes are associated with an increased risk of cerebral palsy. ObjectiveTo investigate associations between inherited cytokine polymorphisms and cerebral palsy in a large population-based case-control study. To investigate associations between inherited cytokine polymorphisms and cerebral palsy in a large population-based case-control study. Study designGenomic DNA from the newborn screening cards of 443 Caucasian CP cases and 883 Caucasian controls was tested for five cytokine polymorphisms: Tumour Necrosis Factor alpha –308 (TNF-alpha-308), Mannose Binding Lectin –221 (MBL –221), and three polymorphisms in Exon 1 of the Mannose Binding Lectin gene at codons 52, 54 and 57. Genomic DNA from the newborn screening cards of 443 Caucasian CP cases and 883 Caucasian controls was tested for five cytokine polymorphisms: Tumour Necrosis Factor alpha –308 (TNF-alpha-308), Mannose Binding Lectin –221 (MBL –221), and three polymorphisms in Exon 1 of the Mannose Binding Lectin gene at codons 52, 54 and 57. ResultsAt all gestational ages MBL codon 52 (homozygous or heterozygous) was associated with an increased risk of developing quadriplegia (OR 2.74, 0.95-6.96), and MBL codon 54 (homozygous or heterozygous) increased the risk of developing diplegia (OR 1.55, 1.03-2.32). For babies born at term, the risk of developing quadriplegia was associated with heterozygous TNF-alpha (OR 1.82, 1.04-3.15), and MBL codon 52 (homozygous or heterozygous OR 3.24, 0.91-9.42). MBL codon 54 (homozygous or heterozygous) was associated with diplegia (OR 2.12, 1.10-4.05). The presence of any polymorphism in MBL exon 1 at term approximately doubled the risk of developing diplegia (OR 1.94, 1.05-3.62). Carriage of an abnormal TNF-alpha allele was associated with hemiplegia for babies born <32 weeks gestation (OR 2.38, 1.02-5.58). Overall, the presence of any cytokine polymorphism was associated with CP (OR 1.37, 95% CI 1.02-1.84). At all gestational ages MBL codon 52 (homozygous or heterozygous) was associated with an increased risk of developing quadriplegia (OR 2.74, 0.95-6.96), and MBL codon 54 (homozygous or heterozygous) increased the risk of developing diplegia (OR 1.55, 1.03-2.32). For babies born at term, the risk of developing quadriplegia was associated with heterozygous TNF-alpha (OR 1.82, 1.04-3.15), and MBL codon 52 (homozygous or heterozygous OR 3.24, 0.91-9.42). MBL codon 54 (homozygous or heterozygous) was associated with diplegia (OR 2.12, 1.10-4.05). The presence of any polymorphism in MBL exon 1 at term approximately doubled the risk of developing diplegia (OR 1.94, 1.05-3.62). Carriage of an abnormal TNF-alpha allele was associated with hemiplegia for babies born <32 weeks gestation (OR 2.38, 1.02-5.58). Overall, the presence of any cytokine polymorphism was associated with CP (OR 1.37, 95% CI 1.02-1.84). ConclusionThe data derived from this large population sample of Caucasian cerebral palsy cases and controls demonstrate that carriage of polymorphisms in the TNF-alpha and MBL genes are associated with an increased risk of cerebral palsy. The data derived from this large population sample of Caucasian cerebral palsy cases and controls demonstrate that carriage of polymorphisms in the TNF-alpha and MBL genes are associated with an increased risk of cerebral palsy.