新疆癫痫患儿HLA-B基因多态性与奥卡西平所致斑丘疹的相关性研究

Relationship between HLA-B gene polymorphism and macular papule caused by oxcarbazepine in epileptic children in Xinjiang

目的:探讨我国新疆癫痫患儿HLA-B基因多态性与奥卡西平(oxcarbazepine,OXC)引起斑丘疹的相关性。方法:收集服用OXC后引起斑丘疹16例和未发生斑丘疹的135例癫痫患儿,采用第二代测序技术对151例癫痫患儿的HLA-B等位基因进行全基因组测序,分析OXC引起的斑丘疹与HLA-B基因多态性的相关性。结果:OXC-MPE组、OXC-耐受组和一般人群的HLA-B*0702基因型频率分别为:28.13%(9/32),2.43%(9/370)和2.14%(103/4816)。HLA-B*0702的等位基因阳性率在OXC-MPE组、OXC-耐受组和一般人群之间的差异均具有统计学意义(P<0.01,OR=26.51,95%CI:4.40~82.58;P<0.01,OR=27.45,95%CI:13.08~57.65)。HLA-B*4032的等位基因阳性率在OXC-MPE组、OXC-耐受组和一般人群之间的差异均具有统计学意义(P<0.05,OR=6.19,95%CI:0.90~0.99)。此外,OXC-MPE组,OXC-耐受组和一般人群的HLA-B*4001基因型频率分别为:0%(0/32),3.78%(14/370)和0.53%(27/5117)。HLA-B*4001的等位基因阳性率在OXC-MPE组和OXC-耐受组之间的差异有统计学意义(P<0.05,OR=4.08,95%CI:1.00~9.08)。结论:我国新疆癫痫患儿中HLA-B*0702和HLA-B*4032等位基因可能是OXC诱发斑丘疹的风险等位基因,其中HLA-B*0702等位基因的风险度较大。

OBJECTIVE To explore the relationship between HLA-B gene polymorphism and macular papule caused by oxcarbazepine in Han epileptic children in Xinjiang.METHODS Sixteen cases of maculopapular eruption(MPE)caused by oxcarbazepine(OXC)and 135 Han epileptic children without MPE were recruited.Next-generation sequencing was employed for sequencing whole genome of HLA-B alleles in 151 epileptic children and correlation between macular papule caused by oxcarbazepine and HLA-B gene polymorphism was analyzed.RESULTS The frequencies of HLA-B*0702 genotypes in OXC-MPE group,OXC-/tolerance group and general population were 28.13%(9/32),2.43%(9/370)and 2.14%(103/4816)respectively.Significant differences existed in positive rate of HLA-B*0702 allele between OXC-MPE group,OXC-tolerance group and general population(P<0.01,OR=26.51,95%CI:4.40-82.58,P<0.01,OR=27.45,95%CI:13.08-57.65).Significant differences existed in positive rate of HLA-B*4032 allele among OXC-MPE group,OXC-tolerance group and general population(P<0.05,OR=6.19,95%CI:0.90-0.99).In addition,the frequencies of HLA-B*4001 genotypes in OXC-MPE group,OXC-tolerance group and general population were 0%(0/32),3.78%(14/370)and 0.53%(27/5117)respectively.Significant difference existed in positive rate of HLA-B*4001 allele between OXC-MPE and OXC-tolerance group(P<0.05,OR=4.08,95%CI:1.00-9.08).CONCLUSION HLA-B*0702 and HLA-B*4032 alleles may be the risk genes of macular papule induced by OXC in epileptic children in Xinjiang and the risk of HLA-B*0702 allele is higher.