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目的探讨BCRP基因+421位点单核苷酸多态性与依非韦伦引起的中枢神经系统不良反应的相关性。方法用病例-对照研究方法,以82例接受依非韦伦治疗并发生中枢神经系统不良反应的的艾滋病患者(CNS组)和90例无中枢神经系统不良反应的艾滋病患者(对照组)为研究对象。通过Taq Man探针SNP基因分型技术对BCRP基因+421位点进行基因分型,比较两组人群基因型分布及频率差异。同时应用HPLC-UV法测定不同基因型人群依非韦伦血浆浓度的差异,确认基因型与依非韦伦血浆浓度的关系。结果 BCRP基因+421位点具有C和A两种等位基因,其中CNS组C、A等位基因频率分别为58.5%、41.5%,对照组C、A等位基因频率分别为70.0%、30.0%,两组A等位基因频率差异有统计学意义(P<0.05,OR=1.65,95%CI 1.06~2.58)。CNS组和对照组患者血浆依非韦伦在组间和不同基因型之间差异均无统计学意义(P>0.05)。结论 BCRP基因+421多态性位点与依非韦伦引起的中枢神经系统不良反应相关。A等位基因是依非韦伦致中枢神经系统不良反应的易感基因。
Objective To investigate the association between BCRP gene +421 single nucleotide polymorphism and central nervous system adverse reactions induced by efavirenz. Methods A case-control study was conducted in 82 AIDS patients (CNS group) and 90 AIDS patients without central nervous system adverse reactions (control group) who were treated with efavirenz and had central nervous system adverse reactions Object Genotypes of BCRP +421 locus were genotyped by Taq Man probe SNP genotyping, and genotype distribution and frequency difference between two groups were compared. At the same time, the difference of plasma concentration of efavirenz in different genotypes was determined by HPLC-UV method to confirm the relationship between genotype and plasma concentration of efavirenz. Results There was C and A alleles at +421 locus in BCRP gene. The frequencies of C allele and A allele in CNS group were 58.5% and 41.5%, respectively. The frequencies of C allele and A allele in control group were 70.0% and 30.0% %. There was significant difference in A allele frequency between the two groups (P <0.05, OR = 1.65, 95% CI 1.06 ~ 2.58). There was no significant difference between groups and between genotypes of efavirenz in the CNS and control groups (P> 0.05). Conclusion BCRP +421 polymorphism is associated with central nervous system reactions caused by efavirenz. The A allele is a predisposing gene to efavirenz leading to central nervous system adverse effects.