目的:研究卡马西平(cabamazepine,CBZ)药品不良反应(adverse drug reactions,ADRs)与遗传因素及血药浓度的关系,以促进CBZ临床安全和合理应用。方法:回顾性收集上海交通大学医学院附属瑞金医院2017-2019年住院患者资料,采集HLA-B*1502...目的:研究卡马西平(cabamazepine,CBZ)药品不良反应(adverse drug reactions,ADRs)与遗传因素及血药浓度的关系,以促进CBZ临床安全和合理应用。方法:回顾性收集上海交通大学医学院附属瑞金医院2017-2019年住院患者资料,采集HLA-B*1502基因检测或CBZ血药浓度检测信息,分析这些患者HLA-B*1502基因型及CBZ血药浓度与ADRs的关系。结果:共纳入148例患者,其中101例进行了HLA-B*1502基因检测,34例患者基因型呈阳性,阳性率33.66%。148例患者中,78例(53.79%)使用CBZ进行治疗,其中有60例(86例次)进行了CBZ血药浓度检测,53例次CBZ血药浓度在推荐的浓度范围之内,占检测例次的61.63%,32例次(37.21%)低于推荐浓度范围。12例患者(15.38%)出现了CBZ相关的ADRs,其中1例HLA-B*1502纯合子突变型患者在服用CBZ后出现了较严重的皮肤ADRs。结论:HLA-B*1502基因型与CBZ皮肤ADRs有密切相关性。CBZ的治疗窗较窄,其ADRs发生率可能与其血药浓度有关。基因检测与血药浓度检测对于提高CBZ使用的安全性具有较重要意义。展开更多
Previous studies have demonstrated a strong association between carbamazepine（CBZ）-induced Stevens-Johnson syndrome（SJS） and HLA-B 1502 in Han Chinese. Here, we extended the study of HLA-B 1502 susceptibility to t...Previous studies have demonstrated a strong association between carbamazepine（CBZ）-induced Stevens-Johnson syndrome（SJS） and HLA-B 1502 in Han Chinese. Here, we extended the study of HLA-B 1502 susceptibility to two different antiepileptic drugs, oxcarbazepine（OXC） and phenobabital（PB）. In addition, we genotyped HLA-B 1511 in a case of CBZ-induced SJS with genotype negative for HLA-B 1502. The presence of HLA-B 1502 was determined using polymerase chain reaction with sequence-specific primers（PCR-SSP）. Moreover, we genotyped HLA-B 1502 in 17 cases of antiepileptic drugs（AEDs）-induced cutaneous adverse drug reactions（cADRs）, in comparison with AEDs-tolerant（n=32） and normal controls（n=38） in the central region of China. The data showed that HLA-B 1502 was positive in 5 of 6 cases of AEDs-induced SJS（4 CBZ, 1 OXC and 1 PB）, which was significantly more frequent than AEDs-tolerant（2/32, 18 CBZ, 6 PB and 8 OXC） and normal controls（3/38）. Compared with AEDs-tolerant and normal controls, the OR for patients carrying the HLA-B 1502 with AEDs-induced SJS was 6.25（95% CI： 1.06–36.74） and 4.86（95% CI： 1.01–23.47）. The sensitivity and specificity of HLA-B 1502 for prediction of AEDs-induced SJS were 71.4%. The sensitivity and specificity of HLA-B 1502 for prediction of CBZ-induced SJS were 60% and 94%. HLA-B 1502 was not found in 11 children with maculopapular exanthema（MPE）（n=9） and hypersensitivity syndrome（HSS）（n=2）. However, we also found one case of CBZ-induced SJS who was negative for HLA-B 1502 but carried HLA-B 1511. It was suggested that the association between the CBZ-induced SJS and HLA-B 1502 allele in Han Chinese children can extend to other aromatic AEDs including OXC and PB related SJS. HLA-B 1511 may be a risk factor for some patients with CBZ-induced SJS negative for HLA-B 1502.展开更多
文摘目的:研究卡马西平(cabamazepine,CBZ)药品不良反应(adverse drug reactions,ADRs)与遗传因素及血药浓度的关系,以促进CBZ临床安全和合理应用。方法:回顾性收集上海交通大学医学院附属瑞金医院2017-2019年住院患者资料,采集HLA-B*1502基因检测或CBZ血药浓度检测信息,分析这些患者HLA-B*1502基因型及CBZ血药浓度与ADRs的关系。结果:共纳入148例患者,其中101例进行了HLA-B*1502基因检测,34例患者基因型呈阳性,阳性率33.66%。148例患者中,78例(53.79%)使用CBZ进行治疗,其中有60例(86例次)进行了CBZ血药浓度检测,53例次CBZ血药浓度在推荐的浓度范围之内,占检测例次的61.63%,32例次(37.21%)低于推荐浓度范围。12例患者(15.38%)出现了CBZ相关的ADRs,其中1例HLA-B*1502纯合子突变型患者在服用CBZ后出现了较严重的皮肤ADRs。结论:HLA-B*1502基因型与CBZ皮肤ADRs有密切相关性。CBZ的治疗窗较窄,其ADRs发生率可能与其血药浓度有关。基因检测与血药浓度检测对于提高CBZ使用的安全性具有较重要意义。
基金supported by a grant from Clinical Scientific Research of Wuhan Sanitary Bureau(No.WX11C26)research fund from Janssen Research Council of China(No.JRCC2011-01)
文摘Previous studies have demonstrated a strong association between carbamazepine（CBZ）-induced Stevens-Johnson syndrome（SJS） and HLA-B 1502 in Han Chinese. Here, we extended the study of HLA-B 1502 susceptibility to two different antiepileptic drugs, oxcarbazepine（OXC） and phenobabital（PB）. In addition, we genotyped HLA-B 1511 in a case of CBZ-induced SJS with genotype negative for HLA-B 1502. The presence of HLA-B 1502 was determined using polymerase chain reaction with sequence-specific primers（PCR-SSP）. Moreover, we genotyped HLA-B 1502 in 17 cases of antiepileptic drugs（AEDs）-induced cutaneous adverse drug reactions（cADRs）, in comparison with AEDs-tolerant（n=32） and normal controls（n=38） in the central region of China. The data showed that HLA-B 1502 was positive in 5 of 6 cases of AEDs-induced SJS（4 CBZ, 1 OXC and 1 PB）, which was significantly more frequent than AEDs-tolerant（2/32, 18 CBZ, 6 PB and 8 OXC） and normal controls（3/38）. Compared with AEDs-tolerant and normal controls, the OR for patients carrying the HLA-B 1502 with AEDs-induced SJS was 6.25（95% CI： 1.06–36.74） and 4.86（95% CI： 1.01–23.47）. The sensitivity and specificity of HLA-B 1502 for prediction of AEDs-induced SJS were 71.4%. The sensitivity and specificity of HLA-B 1502 for prediction of CBZ-induced SJS were 60% and 94%. HLA-B 1502 was not found in 11 children with maculopapular exanthema（MPE）（n=9） and hypersensitivity syndrome（HSS）（n=2）. However, we also found one case of CBZ-induced SJS who was negative for HLA-B 1502 but carried HLA-B 1511. It was suggested that the association between the CBZ-induced SJS and HLA-B 1502 allele in Han Chinese children can extend to other aromatic AEDs including OXC and PB related SJS. HLA-B 1511 may be a risk factor for some patients with CBZ-induced SJS negative for HLA-B 1502.
