[P3-70] Association of a Novel GABRG2 Splicing Variation and a PTGS2/COX-2 Single Nucleotide Polymorphism with Taiwanese Febrile Seizures
The occurrence of febrile seizure (FS) in children with febrile illness suggested genetic factors as an important role on the predisposition of the disease. Using targeted next generation sequencing (NGS), a novel splicing variation (c.1249-1G>T) was identified in the r-aminobutyric acid type A (GABA-A) receptor 2 subunit (GABRG2) gene. To investigate possible association of FS with single nucleotide polymorphisms (SNPs) in prostaglandin-endoperoxide synthase-2 (prostaglandin G/H synthase-2; PTGS2/cyclooxygenase-2; COX2) gene involving in thermoregulatory pathway, eight SNPs, rs689465, rs689466, rs20417, rs13306038, rs201931599, rs689470, rs4648306 and rs4648308, along with 2 previously reported variations in IL1RN (86-bp VNTR) and IL10 (rs1900872) were genotyped and utilized for case-control association studies on 34 FS and 24 non-FS controls. A single SNP (rs689466) localized at 5’ -1192 of the PTGS2 gene exhibited significant association with FS (p=0.045) based on case-control allelic association analyses. A significant decrease in the frequency of the G allele in FS (0.357) was observed compared to that in controls (0.536) with an estimated odds ratio of 0.48 (95% CI, 0.23~0.99) for the G versus A allele. Using case-control genotypic association analysis, the -1192 A allele is most likely to confer susceptibility to FS by a recessive action model (p=0.045, pointwise empirical p value (EMP1)=0.049). The association of SNPs in PTGS2, in addition to IL6, IL-6 receptor (IL6R) and prostaglandin E receptor 3 subtype EP3 (PTGER3) in prior reports, with FS suggests their possible action in concert to modulate phenotypes in FS as well as the involvement of thermoregulatory pathway in pathogenesis of FS.