KCNMA1单核苷酸多态与托吡酯治疗癫痫患儿疗效的相关性分析

Correlation analysis of KCNMA1 single nucleotide polymorphism with the efficacy of topiramate in the treatment of epileptic children

目的:探讨高导钙和电压依赖K+(BK)钾通道的α-亚基(KCNMA1)单核苷酸多态与托吡酯治疗癫痫患儿疗效的相关性。方法:纳入2017年1月至2022年1月河南大学淮河医院收治的癫痫患儿746例,一代测序检测癫痫患儿KCNMA1的基因序列。根据序列,对照组为KCNMA1野生型患儿,突变组为KCNMA1突变型患儿,A138V组为A138V突变患儿,C495G组为C495G突变患儿,N599D组为N599D突变患儿。托吡酯治疗后,分析不同组患儿碱性磷酸酶(ALP)和血钙(SC)水平、疗效及不良反应的差异。结果:746例癫痫患儿中,KCNMA1野生型有660例,突变型有86例。KCNMA1 A138V、C495G、N599D及R800W的频率分别为4.96%、2.95%、1.74%、1.88%。与对照组比较,突变组的治疗有效率更低,差异有统计学意义(P<0.05)。与对照组比较,C495G组的治疗有效率更低(P<0.05)。托吡酯治疗后,与对照组比较,突变组患儿ALP水平更高(P<0.05)。托吡酯治疗后,对照组和突变组患儿SC水平的差异无统计学意义。托吡酯治疗后,与对照组比较,C495G组和R800W组患儿的ALP水平均更高(P<0.05)。与对照组相比,突变组患儿具有更高的不良反应发生率。与对照组相比,A138V组和C495G组患儿具有更高的不良反应发生率。结论:KCNMA1单核苷酸多态C495G和R800W与托吡酯疗效具有相关性,A138V和C495G与托吡酯带来的不良反应具有相关性。

OBJECTIVE To explore the correlation between KCNMA1 single nucleotide polymorphism and the efficacy of topiramate in the treatment of epileptic children. METHODS From January 2017 to January 2022, a total of 746 epileptic children were recruited. According to the gene sequence of KCNMA1, they were assigned into two groups of control(n=660) and mutant(n=86). Control group was composed of KCNMA1 wild-type children while mutant group KCNMA1 mutant children.There were mutations of A138V, C495G and N599D. After topiramate dosing, the inter-group differences of alkaline phosphatase(ALP) and blood calcium(SC) levels, efficacy and adverse reactions were examined. RESULTS The frequencies of KCNMA1 A138V, C495G, N599D and R800W were 4. 96%, 2. 95%, 1. 74% and 1. 88% respectively. As compared with control group, effective rate of mutant group was lower(P<0. 05). As compared with control group, effective rate of C495G group was lower(P<0. 05). After topiramate dosing, ALP level was higher in mutant group than that in control group and the difference was statistically significant. After topiramate dosing, no significant inter-group difference existed in SC level. After topiramate dosing, ALP level was higher in C495G/R800W group than that in control group(P<0. 05). As compared with control group, mutation group had a higher incidence of adverse reactions and the difference was statistically significant(P<0. 05). As compared with control group, A138V and C495G groups had a higher incidence of adverse reactions(P<0. 05).CONCLUSION KCNMA1 single nucleotide polymorphism C495G and R800W are correlated with a definite efficacy of topiramate. And A138V and C495G are correlated with the adverse reactions caused by topiramate.