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抗癲癇藥引起的輕度皮膚過敏反應與中國北方漢族人群HLA基因多態(tài)性的相關(guān)性研究

發(fā)布時間:2019-06-18 11:19
【摘要】:目的:探討抗癲癇藥物引起的輕度皮膚過敏反應與中國北方漢族人群HLA基因多態(tài)性的相關(guān)性。方法:收集2016年8月~2017年3月吉林大學第一醫(yī)院神經(jīng)內(nèi)科門診及病房的26例服用抗癲癇藥出現(xiàn)皮膚過敏反應的患者作為實驗組,同時收集23例服用抗癲癇藥未出現(xiàn)皮膚過敏反應的癲癇患者作為對照組。所有實驗組及對照組患者均行腦電圖、頭MRI或頭CT等相關(guān)檢查,并根據(jù)臨床表現(xiàn)及輔助檢查確診為癲癇,且口服抗癲癇藥。同時采集實驗組及對照組患者的性別、年齡、民族、身高、體重、癲癇發(fā)病年齡、病程、發(fā)作頻率、持續(xù)時間、抗癲癇藥的治療經(jīng)過及不良反應等基本信息,對于實驗組患者記錄其出現(xiàn)皮膚不良反應的時間、皮膚不良反應的分類、對抗過敏藥的治療反應、是否伴有瘙癢等信息。所有實驗組和對照組成員均采集外周血液,利用SBT高分辨率分型檢測技術(shù)測定HLA的A、B兩個位點所有基因型。運用統(tǒng)計學方法分析服用抗癲癇藥物出現(xiàn)的輕度皮膚過敏反應是否與HLA基因多態(tài)性存在相關(guān)性,并分析抗癲癇藥物引起的皮膚過敏反應的臨床特點。結(jié)果:(1)皮膚斑丘疹為抗癲癇藥物引起的最常見的皮膚過敏反應類型。(2)實驗組與對照組HLA分型結(jié)果比較:有1種HLA-A等位基因及7種HLA-B等位基因的OR值大于2,分別為A*0301,B*1301,B*1501,B*1511,B*3701,B*4002,B*4601,B*6701;有3種HLA-A等位基及13種HLA-B等位基因的OR值小于0.5,分別為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。運用Fisher確切概率法對其進行P值計算,發(fā)現(xiàn)所有的HLA-A、B等位基因在實驗組和對照組之間均無統(tǒng)計學差異(P0.05)。(3)芳香族抗癲癇藥引起的輕度皮膚過敏反應患者與對照組的HLA分型結(jié)果比較:有2種HLA-A等位基因及2種HLA-B等位基因的OR值大于2,分別為A*0201,A*3101,B*1301,B*6701;有5種HLA-A等位基因和10種HLA-B等位基因的OR值小于0.5,分別為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。對兩組中所有等位基因進行P值計算,發(fā)現(xiàn)兩組之間并無統(tǒng)計學差異(P0.05)。(4)奧卡西平引起的輕度皮膚過敏反應患者與耐受者的HLA分型結(jié)果對比:有2種HLA-A等位基因及5種HLA-B等位基因的OR值大于2,分別為A*0201,A*3101,B*1501,B*5801,B*6701,B*4002,B*4601;有5種HLA-A等位基因及11種HLAB等位基因的OR值小于0.5,分別為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。對上述等位基因進行P值計算,發(fā)現(xiàn)奧卡西平引起的輕度皮膚過敏反應與HLA-A、B位點的基因多態(tài)性無顯著相關(guān)性(P0.05)。(5)卡馬西平引起的輕度皮膚過敏反應患者與耐受者的HLA分型結(jié)果對比:有4種HLA-A等位基因及6種HLA-B等位基因的OR值大于2,分別為A*0101,A*0201,A*3101,A*6801,B*1301,B*1512,B*3505,B*5601,B*5701,B*3701。有5種HLAA及7種HLA-B等位基因的OR值小于0.5,分別為A*0207,A*2403,A*3201,A*3303,A*0206,B*1501,B*1518,B*3501,B*4006,B*4402,B*5201,B*5801。對上述等位基因進行P值計算,發(fā)現(xiàn)卡馬西平引起的輕度皮膚過敏反應與HLA-A、B位點的基因多態(tài)性無顯著相關(guān)性(P0.05)。(6)左乙拉西坦引起的輕度皮膚過敏反應患者與耐受者的HLA分型結(jié)果對比:有2種HLA-A等位基因及5種HLA-B等位基因的OR值小于0.5,分別為A*0201,A*3101,B*1505,B*3501,B*4001,B*5401,B*1302。對上述等位基因進行P值計算,發(fā)現(xiàn)左乙拉西坦引起的輕度皮膚過敏反應與HLA-A、B位點的基因多態(tài)性無顯著相關(guān)性(P0.05)。(7)實驗組中有瘙癢者和無瘙癢者的HLA分型結(jié)果對比:有3種HLA-A及2種HLAB等位基因的OR值大于2,分別為A*0101,A*2402,A*3101,B*1301,B*3701;3種HLA-A及4種HLA-B等位基因的OR值小于0.5,分別為A*0203,A*1101,A*3001,B*3901,B*4001,B*5201,B*5401。對有上述所有的等位基因進行P值計算,發(fā)現(xiàn)抗癲癇藥物引起的皮膚瘙癢與HLA-A、B位點基因多態(tài)性無顯著相關(guān)性(P0.05)。結(jié)論:抗癲癇藥物引起的輕度皮膚過敏反應與中國北方漢族人群HLA-A、B位點的基因多態(tài)性無顯著相關(guān)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.
【學位授予單位】:吉林大學
【學位級別】:碩士
【學位授予年份】:2017
【分類號】:R742.1;R758.25

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