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 - 2014/6

Y1 - 2014/6

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.

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.

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 - Journal article

C2 - 24703484

AN - SCOPUS:84901950653

VL - 23

SP - 457

EP - 461

JO - Seizure - European Journal of Epilepsy

JF - Seizure - European Journal of Epilepsy

SN - 1059-1311

IS - 6

ER -