Case-control association study of polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, SCN3A, SCN1B, and SCN2B and epilepsy
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摘要High-frequency action potentials are mediated by voltage-gated sodium channels, composed of one large alpha subunit and two small beta subunits, encoded mainly by SCN1A, SCN2A, SCN3A, SCN1B, and SCN2B genes in the brain. These play a key role in epilepsy, with the most commonly mutated gene in epilepsy being SCN1A. We examined whether polymorphisms in the above genes affect epilepsy risk in 1,529 epilepsy patients and 1,935 controls from four ethnicities or locations: Malay, Indian, and Chinese, all from Malaysia, and Chinese from Hong Kong. Of patients, 19 % were idiopathic, 42 % symptomatic, and 40 % cryptogenic. We genotyped 43 polymorphisms: 27 in Hong Kong, 28 in Malaysia, and 12 in both locations. The strongest association with epilepsy was rs3812718, or SCN1A IVS5N+5G > A: odds ratio (OR) = 0.85 for allele G (p = 0.0009) and 0.73 for genotype GG versus AA (p = 0.003). The OR was between 0.76 and 0.87 for all ethnicities. Meta-analysis confirmed the association (OR = 0.81 and p = 0.002 for G, and OR = 0.67 and p = 0.007 for GG versus AA), which appeared particularly strong for Indians and for febrile seizures. Allele G affects splicing and speeds recovery from inactivation. Since SCN1A is preferentially expressed in inhibitory neurons, G may decrease epilepsy risk. SCN1A rs10188577 displayed OR = 1.20 for allele C (p = 0.003); SCN2A rs12467383 had OR = 1.16 for allele A (p = 0.01), and displayed linkage disequilibrium with rs2082366 (r (2) = 0.67), whose genotypes tended toward association with SCN2A brain expression (p = 0.10). SCN1A rs2298771 was associated in Indians (OR = 0.56, p = 0.005) and SCN2B rs602594 with idiopathic epilepsy (OR = 0.62, p = 0.002). Therefore, sodium channel polymorphisms are associated with epilepsy.
著者Baum L, Haerian BS, Ng HK, Wong VCN, Ng PW, Lui CHT, Sin NC, Zhang CB, Tomlinson B, Wong GWK, Tan HJ, Raymond AA, Mohamed Z, Kwan P
期刊名稱Human Genetics
出版年份2014
月份5
日期1
卷號133
期次5
出版社SPRINGER
頁次651 - 659
國際標準期刊號0340-6717
電子國際標準期刊號1432-1203
語言英式英語
Web of Science 學科類別Genetics & Heredity; GENETICS & HEREDITY

上次更新時間 2020-26-11 於 01:09