钠离子通道β1亚单位基因三位点等位基因组合分布与癫痫的相关性

Association between distributions of component genotype of three sites of SCN1B gene and epilepsy

目的分析钠离子通道β1亚单位（SCN1B）基因3个位点（C121W、T189M、R85H）的单核苷酸多态（single nucleotide polymorphisms，SNP）的基因组合分布与癫痫的关系。方法采用等位基因特异性引物PCR技术（ASP—PCR）对SCN1B3个位点SNP进行检测，并用SAS8．1统计软件包对所得数据进行分析。结果从单个位点的基因型来看，癫痫病例组（180例）与健康对照组（150名）3个位点构成在两组间差异具有统计学意义（χ2=11．19、11．14、6．50，P〈0．05），在难治性癫痫组（80例）与非难治性癫痫组（100例）间差异不具有统计学意义（P〉0．05）。从组合基因方面分析，3个位点突变癫痫组为36例（28．80％），高于健康对照组（10名，9．71％），差异具有统计学意义（χ2=12．54，P〈0．01）；难治性癫痫组18例（30．51％），非难治性癫痫组21例（28．77％），差异无统计学意义。2个位点突变的癫痫组50例（40．00％），健康对照组41名（40．20％），差异无统计学意义；难治性癫痫组25例（42．37％），非难治性癫痫组21例（28．71％），差异亦无统计学意义。结论SCN1B基因突变尤其是多个位点突变的人群易患癫痫，基因组合分布在难治性与非难治性癫痫患者中较为相近。

Objective To study the single nucleotide polymorphisms （SNP） in 3 sites allele （T189M, R85H, C121W） of SCNIB and the association between gene distribution and epilepsy. Methods All 330 blood samples of refractory （ 80 cases ）, non-refractory （ 100 cases ） epilepsy patients and healthy people （150 cases） were collected. Genomic DNA of leucocyte was extracted. SNPs of three sites allele of SCN1B were tested by allele-specific primer-polymerase chain reaction （ASP-PCR）. Data were analyzed by SAS 8. 1 statistical software. Results Epilepsy group and healthy group had significantly statistical difference in composition of 3 sites allele on single site genotype （ χ2 = 11.19, 11.14 and 6. 50, all P 〈 0. 05 ）. There was no statistical significance between refractory and non-refractory epilepsy group. On gene combination, in 27 different combinations of polymorphism, mutation frequency in 3 sites （CT ＋ AG ＋ CG） was highest in epilepsy group （ 18.40% ）. The next was one site in CT ＋ GG ＋ CC （ 16. 80% ）. In healthy group, frequency of non-variant in CC ＋ GG ＋ CC was highest （ 16. 67% ）, and the next was 2 sites in CT ＋ AG ＋ CC （ 13.73% ）. Thirty-five cases in epilepsy group （28.80%） had 3 sites mutation compared with 10 cases in healthy group （9. 71% ）, and their difference had statistical significance （χ2= 12, 54, P 〈 0. 05 ）. Eighteen cases in refractory epilepsy group （30. 51% ） had 3 sites mutation compared with 21 cases in non- refractory epilepsy group （28.77%）, and the difference had no statistical significance. Fifty cases in epilepsy group （40. 00% ） had 2 sites mutation compared with 41 cases in healthy group （40. 20% ） , and there was no statistical significance between them; 25 cases in refractory epilepsy group （42. 37% ） had 2 sites mutation compared with 21 cases in non-refractory epilepsy group （28.71%） , and their difference had no statistical significance. Conclusions Mutation, especially multisite mutation of SCN1B is relatively likely to cause epilepsy in human. Gene distribution and combination of three sites allele of SCN1B in refractory epilepsy is close to that in non-refractory epilepsy.