Variations in inflammation-related genes may be associated with childhood febrile seizure susceptibility.
OBJECTIVE
To investigate whether genetic variants in inflammation-related genes are associated with increased risk of childhood-onset febrile seizures.


METHODS
Tagging single nucleotide polymorphisms (SNPs) from 19 inflammation-related candidate genes were identified and genotyped on the Sequenom platform in a sample of Caucasian childhood-onset febrile seizures cases (n=98) compared to ethnicity, age and gender matched febrile controls presenting without seizures (n=123). Tests for allelic association were carried out using PLINK. SNPs generating empirical P-values (P<0.05) were analysed in an expanded Caucasian control sample (n=2692) from the 1958 Birth Cohort.


RESULTS
Six SNPs generated empirical pointwise significance values P<0.05 in the febrile seizures case-control analysis in the P2X7R (purinergic receptor P2X7), TLR4 (toll-like receptor 4), IL6R (interleukin 6 receptor) and PTGER3 (prostaglandin E receptor 3, subtype EP3) genes. The most significant result was for missense SNP rs208294 in P2X7R (P=0.009); this novel association was supported in the expanded case-control analysis using the 1958 Birth Cohort (pointwise P=0.009, OR=0.63, familywise P=0.039).


CONCLUSIONS
Genetic variants in inflammation-related genes, specifically purinergic receptor P2X7, may be involved in susceptibility to childhood-onset febrile seizures.
Department of Neurology, Preston, UK; School of Medicine, University of Liverpool, UK; School of Medicine, University of Manchester, UK. Electronic address: hedley.emsley@manchester.ac.uk.
Hedley C A
HC
Emsley
Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
Richard E
RE
Appleton
Institute of Ageing and Chronic Disease, University of Liverpool, UK.
Catherine L
CL
Whitmore
Centre for Integrated Genomic Medical Research, Manchester Academic Health Science Centre, University of Manchester, UK.
Francine
F
Jury
Centre for Integrated Genomic Medical Research, Manchester Academic Health Science Centre, University of Manchester, UK.
Janine A
JA
Lamb
Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
Joanne E
JE
Martin
Centre for Integrated Genomic Medical Research, Manchester Academic Health Science Centre, University of Manchester, UK.
William E R
WE
Ollier
Department of Emergency Medicine, Central Manchester University Hospitals NHS Foundation Trust, UK.
Katherine Potier
KP
de la Morandière
Institute of Translational Medicine, University of Liverpool, UK.
Kevin W
KW
Southern
Faculty of Life Sciences, University of Manchester, UK.
Stuart M
SM
Allan
D016022:Case-Control Studies; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D019947:Receptors, Interleukin-6 / Q000235:genetics; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000235:genetics; D058486:Receptors, Purinergic P2X7 / Q000235:genetics; D003294:Seizures, Febrile / Q000235:genetics* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics; D044465:White People / Q000235:genetics
C508603:IL6R protein, human; C545647:PTGER3 protein, human; D019947:Receptors, Interleukin-6; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058486:Receptors, Purinergic P2X7; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
Case–control association study; Febrile seizures; Inflammation-related genes; Purinergic receptor P2X7