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. 2015 Apr 13;10(4):e0124896.
doi: 10.1371/journal.pone.0124896. eCollection 2015.

Common variants of KCNJ10 are associated with susceptibility and anti-epileptic drug resistance in Chinese genetic generalized epilepsies

Yong Guo  1 , Kui Po Yan  2 , Qiang Qu  3 , Jian Qu  4 , Zi Gui Chen  1 , Tao Song  1 , Xiang-Ying Luo  1 , Zhong-Yi Sun  1 , Chang-Long Bi  1 , Jin-Fang Liu  1
Affiliations

Common variants of KCNJ10 are associated with susceptibility and anti-epileptic drug resistance in Chinese genetic generalized epilepsies

Yong Guo et al. PLoS One. .

Abstract

To explore genetic mechanism of genetic generalized epilepsies (GGEs) is challenging because of their complex heritance pattern and genetic heterogeneity. KCNJ10 gene encodes Kir4.1 channels and plays a major role in modulating resting membrane potentials in excitable cells. It may cause GGEs if mutated. The purpose of this study was to investigate the possible association between KCNJ10 common variants and the susceptibility and drug resistance of GGEs in Chinese population. The allele-specific MALDI-TOF mass spectrometry method was used to assess 8 single nucleotide polymorphisms (SNPs) of KCNJ10 in 284 healthy controls and 483 Chinese GGEs patients including 279 anti-epileptic drug responsive patients and 204 drug resistant patients. We found the rs6690889 TC+TT genotypes were lower frequency in the GGEs group than that in the healthy controls (6.7% vs 9.5%, p = 0.01, OR = 0.50[0.29-0.86]). The frequency of rs1053074 G allele was lower in the childhood absence epilepsy (CAE) group than that in the healthy controls (28.4% vs 36.2%, p = 0.01, OR = 0.70[0.53-0.93]). The frequency of rs12729701 G allele and AG+GG genotypes was lower in the CAE group than that in the healthy controls (21.2% vs 28.4%, p = 0.01, OR = 0.74[0.59-0.94] and 36.3% vs 48.1%, p = 0.01, OR = 0.83[0.72-0.96], respectively). The frequency of rs12402969 C allele and the CC+CT genotypes were higher in the GGEs drug responsive patients than that in the drug resistant patients (9.3% vs 5.6%, OR = 1.73[1.06-2.85], p = 0.026 and 36.3% vs 48.1%, p = 0.01, OR = 0.83[0.72-0.96], respectively). This study identifies potential SNPs of KCNJ10 gene that may contribute to seizure susceptibility and anti-epileptic drug resistance.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Linkage disequilibrium of 7 tagSNPs in KCNJ10.
Linkage disequilibriums between pairs of polymorphisms are shown with diamonds (r2), with darker shading indicating greater r2.
Fig 2
Fig 2. Frequencies of the haplotypes (>3%) containing all of the tagSNPs of KCNJ10 in the drug-resistant (n = 204) and drug-responsive GGE patients (n = 279).
Fig 3
Fig 3. Significant different frequencies of KCNJ10 haplotypes between the GGEs subtypes and the healthy controls.
See this image and copyright information in PMC

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