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Joint Analysis of SNPs and Proteins Identifies Regulatory IL18 Gene Variations Decreasing the Chance of Spastic Cerebral Palsy

Authors


  • Communicated by A. Jamie Cuticchia

Correspondence to: Mads Vilhelm Hollegaard, Department of Clinical Biochemistry and Immunology, Section of Neonatal Screening and Hormones, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen, Denmark. E-mail: mvh@ssi.dk

Abstract

Cerebral palsy (CP) is a permanent disorder, affecting 2–3 per 1,000 live born children, disturbing movement and posture. Spastic limbs affects about 70–80% of the CP children, and this group is the target of our study. CP is considered a multifactorial condition believed to be provoked by, for example, preterm birth, infection during pregnancy, neural disorders, and genetics, to mention some. Interestingly, the cytokine network is believed to be involved in many of these disorders. In this study, including 203 spastic CP cases and 167 controls, we measured the levels of 25 cytokine proteins, and genotyped 159 SNPs in their gene loci. Using logistic regression, we estimated the genetic association of SNP genotypes to spastic CP. In addition, fitting a Tobit regression model for each protein and each SNP in the respective gene loci, we estimated three regression coefficients corresponding three different effects of the genetic variation on the protein level. Intriguingly, two IL18 loci SNPs (rs549908:A>C and rs1290349:C>A) showed a protective effect against spastic CP, and interestingly both were associated to a decreased epidemiological expression of IL-18 protein. By joining protein data to genetic information, we have provided new data suggesting IL18's involvement in the pathogenesis of spastic CP.

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