GABAARG2基因C588T多态性与癫痫的相关性研究

Association study between the C588T polymorphism of GABAARG2 gene and epilepsy

目的探讨中国粤西地区汉族人群GABAARG2基因C588T的单核苷酸多态性与癫痫的关系。方法采用病例-对照研究方法,收集粤西地区汉族人群189例癫痫患者,100例健康人作为正常对照组,根据患者对抗癫痫药物的反应性分为耐药组（92例）和药物敏感组（97例）,提取所有研究对象外周血基因组DNA,采用PCR扩增后基因测序鉴定GABAARG2基因C588T多态性,测定该位点基因型频率和等位基因频率,并进行统计学分析。结果耐药组与药物敏感组、正常对照组的CC、CT、TT基因型频率及C、T等位基因频率比较差异均无统计学意义;药物敏感组与正常对照组的CC、CT、TT基因型频率比较（χ~2=6.468,P=0.039）差异有统计学意义,CC与CT优势比为1.669（95%CI=0.842~3.306,P=0.141）,CC与TT的优势比为2.652（95%CI=1.240~5.668,P=0.011）;C、T等位基因频率比较（χ~2=7.411,P=0.006）差异有统计学意义,C等位基因与T等位基因优势比为1.737（95%CI=1.166~2.588,P=0.006）。结论 GABAARG2基因5号外显子的C588T多态性与癫痫的易感性相关,但与癫痫的耐药风险不相关。

Objective To investigate the association between the C588T polymorphism of GABAARG2 gene and drug-resistant epilepsy in Chinese Han population of the Western Guangdong province. Methods 189 patients with epilepsy were classified into drug-resistant group（ n = 92） and drug-responsive group（ n = 97）,according to their responses of antiepileptic drug treatment,and 100 healthy controls were chosen as normal control group. DNA samples were obtained from all these people,the C588T polymorphism of GABAARG2 gene was determined by polymerase chain reaction（ PCR） and Gene sequencing. The genotype and allele frequency of the C588T among the three groups was analyzed by Chi-square test.Results No significant differences of genotype frequencies and allele frequencies were identified between the drug-resistant group and drug sensitive group,while no significant differences of genotype frequencies and allele frequencies were identified between the drug-resistant group and normal control group. Significant differences of genotype frequencies were identified between the drug sensitive group and normal control group（ χ~2= 6. 468,P = 0. 039）. CC vs CT OR = 1. 669（ 95% CI =0. 842 ~ 3. 306,P = 0. 141）,CC vs TT OR = 2. 652（ 95% CI = 1. 240 ~ 5. 668,P = 0. 011）,Significant differences of allele frequencies were identified between the drug sensitive group and normal control group（ χ~2= 7. 411,P = 0. 006）,C vs T OR= 1. 737（ 95% CI = 1. 166 ~ 2. 588,P = 0. 006）. Conclusion The C588T polymorphism of GABAARG2 gene is associated with epilepsy susceptibility,but not with antiepileptic drug resistance in Chinese Han population.