抗癫痫药引起的轻度皮肤过敏反应与中国北方汉族人群HLA基因多态性的相关性研究

发布时间：2019-06-18 11:19

【摘要】：目的:探讨抗癫痫药物引起的轻度皮肤过敏反应与中国北方汉族人群HLA基因多态性的相关性。方法:收集2016年8月~2017年3月吉林大学第一医院神经内科门诊及病房的26例服用抗癫痫药出现皮肤过敏反应的患者作为实验组,同时收集23例服用抗癫痫药未出现皮肤过敏反应的癫痫患者作为对照组。所有实验组及对照组患者均行脑电图、头MRI或头CT等相关检查,并根据临床表现及辅助检查确诊为癫痫,且口服抗癫痫药。同时采集实验组及对照组患者的性别、年龄、民族、身高、体重、癫痫发病年龄、病程、发作频率、持续时间、抗癫痫药的治疗经过及不良反应等基本信息,对于实验组患者记录其出现皮肤不良反应的时间、皮肤不良反应的分类、对抗过敏药的治疗反应、是否伴有瘙痒等信息。所有实验组和对照组成员均采集外周血液,利用SBT高分辨率分型检测技术测定HLA的A、B两个位点所有基因型。运用统计学方法分析服用抗癫痫药物出现的轻度皮肤过敏反应是否与HLA基因多态性存在相关性,并分析抗癫痫药物引起的皮肤过敏反应的临床特点。结果:(1)皮肤斑丘疹为抗癫痫药物引起的最常见的皮肤过敏反应类型。(2)实验组与对照组HLA分型结果比较:有1种HLA-A等位基因及7种HLA-B等位基因的OR值大于2,分别为A*0301,B*1301,B*1501,B*1511,B*3701,B*4002,B*4601,B*6701;有3种HLA-A等位基及13种HLA-B等位基因的OR值小于0.5,分别为A*0207,A*2403,A*2601,B*1505,B*1518,B*3501,B*3503,B*3801,B*4403,B*4003,B*4613,B*4801,B*5102,B*5504,B*1510,B*5201。运用Fisher确切概率法对其进行P值计算,发现所有的HLA-A、B等位基因在实验组和对照组之间均无统计学差异(P0.05)。(3)芳香族抗癫痫药引起的轻度皮肤过敏反应患者与对照组的HLA分型结果比较:有2种HLA-A等位基因及2种HLA-B等位基因的OR值大于2,分别为A*0201,A*3101,B*1301,B*6701;有5种HLA-A等位基因和10种HLA-B等位基因的OR值小于0.5,分别为A*0206,A*0207,A*2403,A*2601,A*3303,B*1510,B*1518,B*3503,B*3801,B*4003,B*4613,B*5102,B*5504,B*3501,B*4403。对两组中所有等位基因进行P值计算,发现两组之间并无统计学差异(P0.05)。(4)奥卡西平引起的轻度皮肤过敏反应患者与耐受者的HLA分型结果对比:有2种HLA-A等位基因及5种HLA-B等位基因的OR值大于2,分别为A*0201,A*3101,B*1501,B*5801,B*6701,B*4002,B*4601;有5种HLA-A等位基因及11种HLAB等位基因的OR值小于0.5,分别为A*0101,A*0207,A*1101,A*2601,A*3303,B*4006,B*1510,B*3501,B*3503,B*3701,B*3801,B*4003,B*4613,B*5102,B*5504,B*4403。对上述等位基因进行P值计算,发现奥卡西平引起的轻度皮肤过敏反应与HLA-A、B位点的基因多态性无显著相关性(P0.05)。(5)卡马西平引起的轻度皮肤过敏反应患者与耐受者的HLA分型结果对比:有4种HLA-A等位基因及6种HLA-B等位基因的OR值大于2,分别为A*0101,A*0201,A*3101,A*6801,B*1301,B*1512,B*3505,B*5601,B*5701,B*3701。有5种HLAA及7种HLA-B等位基因的OR值小于0.5,分别为A*0207,A*2403,A*3201,A*3303,A*0206,B*1501,B*1518,B*3501,B*4006,B*4402,B*5201,B*5801。对上述等位基因进行P值计算,发现卡马西平引起的轻度皮肤过敏反应与HLA-A、B位点的基因多态性无显著相关性(P0.05)。(6)左乙拉西坦引起的轻度皮肤过敏反应患者与耐受者的HLA分型结果对比:有2种HLA-A等位基因及5种HLA-B等位基因的OR值小于0.5,分别为A*0201,A*3101,B*1505,B*3501,B*4001,B*5401,B*1302。对上述等位基因进行P值计算,发现左乙拉西坦引起的轻度皮肤过敏反应与HLA-A、B位点的基因多态性无显著相关性(P0.05)。(7)实验组中有瘙痒者和无瘙痒者的HLA分型结果对比:有3种HLA-A及2种HLAB等位基因的OR值大于2,分别为A*0101,A*2402,A*3101,B*1301,B*3701;3种HLA-A及4种HLA-B等位基因的OR值小于0.5,分别为A*0203,A*1101,A*3001,B*3901,B*4001,B*5201,B*5401。对有上述所有的等位基因进行P值计算,发现抗癫痫药物引起的皮肤瘙痒与HLA-A、B位点基因多态性无显著相关性(P0.05)。结论:抗癫痫药物引起的轻度皮肤过敏反应与中国北方汉族人群HLA-A、B位点的基因多态性无显著相关性。
[Abstract]:Objective: To study the relationship between the mild skin allergy caused by antiepileptic drugs and the polymorphism of HLA gene in Chinese Han population. Methods: In the first hospital of the first hospital of Jilin University from August 2016 to March 2017,26 patients taking anti-epileptic drugs in the department of neurology and in the ward were treated as the experimental group, and 23 patients with epilepsy with no skin allergy were collected as the control group. All the experimental groups and the control group were examined by EEG, head MRI or head CT, and were diagnosed with epilepsy according to the clinical manifestation and the auxiliary examination, and the antiepileptic drugs were taken orally. meanwhile, the basic information such as the sex, the age, the nationality, the height, the weight, the age, the course of the disease, the frequency of the attack, the duration, the treatment of the antiepileptic drugs, the adverse reaction and the like of the experimental group and the control group are also collected, In the experimental group, the time of the adverse reaction of the skin, the classification of the adverse reaction of the skin, the treatment response to the allergic drug, and the itching and other information were recorded. The peripheral blood was collected from all the experimental groups and the control group, and all the genotypes of the two sites of A and B were determined by using the high-resolution type detection technique of SBT. A statistical method was used to analyze the relationship between the mild skin allergic reaction and the polymorphism of the HLA gene, and to analyze the clinical characteristics of the skin-allergic reaction caused by the anti-epileptic drugs. Results: (1) The most common type of skin-sensitive reaction caused by skin macula is the antiepileptic drug. (2) The results of HLA typing of the experimental group and the control group were as follows: the OR value of one HLA-A allele and seven HLA-B alleles was greater than 2, A * 0301, B * 1301, B * 1501, B * 1511, B * 3701, B * 4002, B * 4601, B * 6701, and the OR values of three HLA-A alleles and 13 HLA-B alleles were less than 0.5, A * 0207 and A * 2403, respectively. A*2601,B*1505,B*1518,B*3501,B*3503,B*3801,B*4403,B*4003,B*4613,B*4801,B*5102,B*5504,B*1510,B*5201. The P-value was calculated by Fisher's exact probability method, and all HLA-A and B alleles were found to have no statistical difference between the experimental group and the control group (P0.05). (3) The results of HLA typing in the patients with mild skin allergy caused by aromatic antiepileptic drugs were compared with that of the control group: the OR values of the two HLA-A alleles and the two HLA-B alleles were greater than 2, A * 0201, A * 3101, B * 1301, B * 6701, respectively; The OR values of five HLA-A alleles and 10 HLA-B alleles are less than 0.5, A * 0206, A * 0207, A * 2403, A * 2601, A * 3303, B * 1510, B * 1518, B * 3503, B * 3303, B * 4003, B * 4613, B * 5102, B * 5504, B * 3501, B * 4403, respectively. The P-value of all the alleles in the two groups was calculated, and there was no statistical difference between the two groups (P0.05). (4) The results of HLA typing of the patients with mild skin allergy caused by oxcarbazepine were as follows: the OR values of two HLA-A alleles and 5 HLA-B alleles were greater than 2, A * 0201, A * 3101, B * 1501, B * 5801, B * 6701, B * 4002, B * 4601, respectively; The OR values of five HLA-A alleles and 11 HLAB alleles are less than 0.5, A * 0101, A * 0207, A * 1101, A * 2601, A * 3303, B * 4006, B * 1510, B * 3501, B * 3503, B * 3701, B * 3501, B * 4003, B * 4613, B * 5102, B * 5504, B * 4403, respectively. The P-value of the above-mentioned allele was calculated, and it was found that the mild skin-allergic reaction caused by oxcarbazepine had no significant correlation with the gene polymorphism of HLA-A and B sites (P0.05). (5) The results of HLA typing of the patients with mild skin allergy caused by carbamazepine were as follows: the OR values of four HLA-A alleles and 6 HLA-B alleles were greater than 2, A * 0101, A * 0201, A * 3101, A * 6801, B * 1301, B * 1512, B * 3505, B * 5601, B * 5701, B * 3701, respectively. The OR values of five types of HLA-B alleles are less than 0.5, A * 0207, A * 2403, A * 3201, A * 3303, A * 0206, B * 1501, B * 1518, B * 3501, B * 4006, B * 4402, B * 5201, B * 5801, respectively. The P-value of the above-mentioned allele was calculated, and it was found that the mild skin-allergic reaction caused by carbamazepine had no significant correlation with the gene polymorphism of HLA-A and B sites (P0.05). (6) The results of HLA typing of the patients with mild skin allergy caused by levetiracetam: the OR values of the two HLA-A alleles and the five HLA-B alleles were less than 0.5, A * 0201, A * 3101, B * 1505, B * 3501, B * 4001, B * 5401, and B * 1302 respectively. The P-value of the above-mentioned allele was calculated, and there was no significant correlation between the reaction of the mild skin allergy caused by levetiracetam and the polymorphism of the HLA-A and B sites (P0.05). (7) There were three HLA-A and 2 types of HLA-B alleles with OR values greater than 2, A * 0101, A * 2402, A * 3101, B * 1301, B * 3701, and the OR values of HLA-A and 4 HLA-B alleles were less than 0.5, A * 0203, A * 1101, A * 3001, B * 3901, B * 4001, B * 5201, respectively. B*5401. The results showed that there was no significant correlation between the polymorphism of HLA-A and B sites in anti-epileptic drugs (P0.05). Conclusion: The mild skin allergy caused by antiepileptic drugs has no significant correlation with the genetic polymorphisms of HLA-A and B sites in the Chinese Han population.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R742.1;R758.25

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