Association study between polymorphisms in the CACNA1A, CACNA1C, and CACNA1H genes and drug-resistant epilepsy in the Chinese Han population

• We provide the first worldwide association study.
• We found no association between SNPs of CACNA1A, 1C, and 1H and drug-resistant epilepsy.
• We calculated a meaningful haplotype of CACNA1A.

PurposeAs important ion channels of the central nervous system, calcium channels not only take part in epileptogenesis but also act as the targets of commonly used antiepileptic drugs (AEDs). Thus, this study aimed to provide the first investigation of the association between CACNA1A, CACNA1C, and CACNA1H single nucleotide polymorphisms (SNPs) and AED resistance in the Chinese Han population.MethodsWe performed genotyping of tagging single nucleotide polymorphisms (tagSNPs) of CACNA1A, 1C and 1H in 480 Chinese epilepsy patients (288 drug-responsive and 192 drug-resistant patients). The Illumina GoldenGate BeadArray assay was used to detect the genotypes of all of the patients. A total of 15 SNPs were selected based on the HapMap database. The genotype distributions in drug-responsive and drug-resistant patients were compared, and the haplotype frequencies of each gene were calculated.ResultsNone of the 15 tagSNPs alleles were found to be associated with drug-resistant epilepsy. However, the frequency of the TAGAA haplotype in CACNA1A was significantly higher in drug-resistant patients than in drug-responsive patients after the correction of multiple comparisons with Bonferroni's method (TAGAA 13.3% vs. 7.1%, OR = 2.129 [1.373–3.299], P = 0.00059 < 0.05/10).ConclusionsThis study revealed no association between the 15 tagSNPs of CACNA1A, 1C, and 1H and drug efficacy in the Chinese Han population. The TAGAA haplotype of CACNA1A may be a risk factor for AED resistance.