Supplementary Material for: Cerebral Palsy and Polymorphism of the Chemokine <b><i>CCL18</i></b> in Very Preterm Children

<b><i>Background:</i></b> Prematurity and hereditary factors predispose to cerebral palsy (CP).<b> </b>Previously, low cord blood levels of the anti-inflammatory chemokine CCL18 have been found to be associated with risk of CP in preterm children. <b><i>Objectives:</i></b> To investigate the association between single nucleotide polymorphisms (SNPs) in <i>CCL18</i> and susceptibility to CP, as well as the association between the SNPs and cord blood levels of CCL18. <b><i>Methods:</i></b> The original population comprised very-low-gestational-age (VLGA; <32 weeks) children from northern and central Finland (25 cases, 195 controls). Five <i>CCL18</i> SNPs were genotyped and examined for associations with CP and cord blood CCL18. The replication population comprised Caucasian VLGA children from southern Finland and Canada (23 cases, 248 controls). <b><i>Results:</i></b> In the original population, SNP rs2735835 was associated with CP; the minor allele A was underrepresented in cases compared to controls (OR = 0.42, 95% CI: 0.21-0.83, p = 0.01). This association remained significant after adjustment for multiple testing and risk factors of CP, and after combining the original and replication populations (OR = 0.52, 95% CI: 0.33-0.83, p = 0.005). Intraventricular hemorrhage (IVH) additively predicted CP. The Rs2015086 genotype was modestly associated with CCL18 concentration. <b><i>Conclusions:</i></b> A common <i>CCL18 </i>polymorphism together with IVH had an additive influence on CP susceptibility. Developmentally regulated <i>CCL18,</i> confined to primates, may be involved in the complex sequence of events leading to brain injury and predisposition to CP phenotype.