Relationship between the single nucleotide polymorphisms of SCN1A genes and the therapeutic effects of carbamazepine in Zhuang population with epilepsies / 实用医学杂志

ABSTRACT

Objective To investigate the relationship between the single nucleotide polymorphisms of SCN1A genes and the therapeutic effects of carbamazepine in Zhuang population with epilepsies. Methods We used Mass ARRAY-IPLEX and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) technology to detect the SCN1A gene rs4667869 and rs10497275 genotypes in peripheral blood of186 Zhuang individuals with epileptic (66 cases in effective group and 120 cases of ineffective group) who received the standardized treatment of carbamazepine in Baise Region. The reversed phase high-performance liquid chromatography was used to determine blood drug level of carbamazepine. The correlations between the genotypes, alleles and the carbamazepine efficacy of the two groups were evaluated, respectively. We also analyzed the difference of carbamazepine's blood concentration between different genotypes. Results Three genotypes of GG, GC and CC were detected in rs4667869 locus. There were 3 genotypes of GG, GA and AA found in rs 10497275 locus.The differences in the allele distribution (χ2 = 11.790, P = 0.001) and genotype distribution (χ2= 10.655, P =0.005) of the rs4667869 locus were statistically significant between the two groups (ineffective group vs. effective group). However, there was no significant difference in allele distribution (χ2 = 3.335, P= 0.068) and genotype (χ2= 3.046, P = 0.218) for rs 10497275 locus in these two groups. Compared with the GG + GC genotype, the CC genotype of rs4667869 locus significantly reduced the antiepileptic efficacy of carbamazepine (OR = 2.800, 95％CI 1.495～5.244). W hile there were no significant differences in blood concentration of genotype CC (t=1.273, P = 0.083) comparing with genotypes GG + GC in rs4667869. No significant differences were found in blood concentration between genotype AA and genotypes GG + GA of rs 10497275 (t= 0.963, P = 0.064). Conclusions These results suggest that the single nucleotide polymorphisms of rs4667869 in SCN1A genes could be associated with the drug resistance of carbamazepine in Zhuang population with epilepsies.