TY - JOUR
T1 - Variations in inflammation-related genes may be associated with childhood febrile seizure susceptibility
AU - Emsley, Hedley C A
AU - Appleton, Richard E.
AU - Whitmore, Catherine L.
AU - Jury, Francine
AU - Lamb, Janine A.
AU - Martin, Joanne E.
AU - Ollier, William E R
AU - De La Morandière, Katherine Potier
AU - Southern, Kevin W.
AU - Allan, Stuart M.
PY - 2014
Y1 - 2014
N2 - Purpose To investigate whether genetic variants in inflammation-related genes are associated with increased risk of childhood-onset febrile seizures. Method 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). Conclusion Genetic variants in inflammation-related genes, specifically purinergic receptor P2X7, may be involved in susceptibility to childhood-onset febrile seizures. © 2014 British Epilepsy Association.
AB - Purpose To investigate whether genetic variants in inflammation-related genes are associated with increased risk of childhood-onset febrile seizures. Method 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). Conclusion Genetic variants in inflammation-related genes, specifically purinergic receptor P2X7, may be involved in susceptibility to childhood-onset febrile seizures. © 2014 British Epilepsy Association.
KW - Case-control association study
KW - Febrile seizures
KW - Inflammation-related genes
KW - Purinergic receptor P2X7
U2 - 10.1016/j.seizure.2014.03.006
DO - 10.1016/j.seizure.2014.03.006
M3 - Article
C2 - 24703484
SN - 1059-1311
VL - 23
SP - 457
EP - 461
JO - Seizure: European Journal of Epilepsy
JF - Seizure: European Journal of Epilepsy
IS - 6
ER -