Background Cerebral palsy (CP) is a nonprogressive motor impairment syndrome caused by damage in the developing brain and it reveals clustering to preterm infants. Recently, genetic factors have been suggested as risk modifiers for CP. However, the individual genes causing predisposition to CP are still poorly understood. Low cord blood levels of CCL18 have been found to associate with CP in preterm infants. Since CCL18 gene is restricted to primates, it may be considered as a candidate for functionality in human brain.
Aims To investigate the association between the CCL18 gene single nucleotide polymorphisms (SNPs) and the cord blood levels of CCL18. Further to study the association between the CCL18 SNPs and the susceptibility to CP.
Methods A prospective cohort consisted of 161 children born very preterm (gestation < 32 weeks) in Oulu University Hospital during 1997–2006. Concentration of the cord blood CCL18 was analysed (n=99). Five CCL18 SNPs (rs1102934, rs2015086, rs2015070, rs2735835, rs712044) were genotyped. Cerebral palsy was confirmed at 5 years of age.
Results Two CCL18 SNPs associated with CCL18 (P=0.011; P=0.039). Additionally, CCL18 (SNP rs2735835) associated with CP. Thus, CP occurred in 11 (18%) of 61 children with GG genotype compared with 6 (6%) of 100 children with AA/GA genotype (OR 4.1; 95% CI 1.3–12.5, P=0.013).
Conclusions Variation of the CCL18 gene associates with CCL18 concentration and with predisposition to CP in very preterm infants. This is consistent with the hypothesis that CCL18 has a role in the complex sequence leading to brain damage.