The genomic basis of cerebral palsy: a HuGE systematic literature review

• Published in: Human genetics 2009-07, Vol.126 (1), p.149-172
• Main Authors: O’Callaghan, M. E., MacLennan, A. H., Haan, E. A., Dekker, G.
• Format: Article
• Language: English
• Subjects: Apolipoproteins; Apolipoproteins E - genetics; Biomedical and Life Sciences; Biomedicine; Blood coagulation factors; Case-Control Studies; Cerebral palsy; Cerebral Palsy - genetics; Chromosomes; Cohort Studies; Cytokines; Databases, Factual; Factor V - genetics; Forecasting; Gene Function; Genes; Genetic aspects; Genomes; Genotype & phenotype; Guidelines as Topic; Haplotypes; Human Genetics; Humans; Literature reviews; Lymphotoxin-alpha - genetics; Mannose-Binding Lectin - genetics; Metabolic Diseases; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Molecular Medicine; Mutation; Nitric Oxide Synthase Type III - genetics; Physiology; Polymorphism; Polymorphism, Single Nucleotide; Proteins; Review Article; Single nucleotide polymorphisms; Systematic review; Thrombosis; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-TNF
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-009-0638-5

Cerebral palsy has been associated with a number of candidate genes. To date, no systematic review has been conducted to synthesise genetic polymorphism associations with cerebral palsy. We apply the HuGE NET guidelines to search PubMed and EMBASE databases for publications investigating single nucleotide polymorphisms (SNPs) and cerebral palsy outcome. 22 papers were identified and are discussed in this review. Candidate genes were grouped as (1) thrombophilic, (2) cytokine, (3) apolipoprotein E or (4) other SNPs, largely related to cardiovascular physiology/pathophysiology and the functioning of the immune system. Of the studies identified, cohorts were usually small, without adequate control and ethnically diverse, making direct comparison between studies difficult. The most promising candidate genes include factor V Leiden, methylenetetrahydrofolate reductase, lymphotoxin-α, tumour necrosis factor-α, eNOS and mannose binding lectin. Large case–control studies are needed to confirm these candidates with attention given to cohort ethnicity, cerebral palsy subtype analysis and possible multiple gene and gene–environment interactions.