In:
Clinical and Experimental Pharmacology and Physiology, Wiley, Vol. 45, No. 3 ( 2018-03), p. 226-233
Abstract:
Epilepsy is a common complex neurological disorder, and some forms are resistant to drug treatment. The HCN 1 / HCN 2 genes encode hyperpolarization‐activated cyclic nucleotide‐gated channels, which play important roles in the electrophysiology of neurons. We investigated the association between HCN 1 / HCN 2 variants and drug resistance or the risk of genetic generalized epilepsies ( GGE s). We used matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry to assess nine variants of HCN 1 / HCN 2 in 284 healthy participants and 483 GGE s (279 drug‐responsive, 204 drug‐resistant). Frequencies of HCN 2 rs7255568 and rs3752158 G alleles differed in GGE s and in controls ( P = .039, P = .027, respectively). The frequency of HCN 2 haplotype ( CAC ) was higher in patients than controls ( P = .046). The frequency of the HCN 1 rs10462087 CC + CT genotype was lower in patients with childhood absence epilepsy ( CAE ) than controls ( P = .047). Rs7255568 was associated with the risk of CAE ( P = .028) and juvenile myoclonic epilepsy ( JME ) ( P = .02). Rs3752158 was associated with the risk of generalized tonic‐clonic seizures, JME , and febrile seizures (all P 〈 .05). The frequency of the HCN 2 haplotype ( CAC ) was higher in patients with JME ( P = .015) and in those with febrile seizures ( P = .024) than in controls. No significant association was found between HCN 1 / HCN 2 alleles, genotypes or haplotypes, and drug resistance in patients. After Bonferroni's multiple comparisons correction, only the HCN 2 rs3752158 C allele and GC + CC genotype frequencies in patients with JME were higher than those in controls (19.2% vs 11.6%, odds ratio ( OR ) = 1.71, 95% CI = 1.18‐2.32), P = .004 〈 0.05/9; 36% vs 22.2%, OR = 1.62(1.18‐2.23), P = .003 〈 0.05/9). Our study suggests that HCN 2 rs3752158 is involved in the susceptibility to JME .
Type of Medium:
Online Resource
ISSN:
0305-1870
,
1440-1681
DOI:
10.1111/cep.2018.45.issue-3
DOI:
10.1111/1440-1681.12877
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2020033-X
SSG:
15,3
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