The Association Between Antiepileptic Drugs-induced Mild Cutaneous Adverse Reaction And HLA Gene Polymorphism In A Northern Han Chinese Population

Objective:To explore the correlation about antiepileptic drugs-induced mild cutaneous adverse reaction and HLA gene polymorphism in a northern Han Chinese poplation.Methods:Collected from August 2016 to March 2017,26 cases of patients with antiepileptic drugsinduced mild cutaneous adverse reaction in the neurology Department,No1 Hospital of Jilin University,as the experimental group.At the same time,23 epilepsy patients without skin adverse reaction after taking antiepileptic drugs were collected as normal control group.All patients in the experimental group and normal control group performed EEG,head MRI or CT examination and other related texts,diagnosed as epilepsy according to the clinical features then take oral antiepileptic drugs.Meanwhile,we collected the information about age,gender,nationality,height,weight,epilepsy onset age,seizure duration,seizure frequency,antiepileptic treatment process and related adverse reactions etc.In the experimental group,we also collected some information about cutaneous adverse reaction,such as the occurrence time,classification,response to antiallergic drug and whether accompanied with itch.Then peripheral blood sample was taken from each group,genetic technology was applied to detect the HLA gene type.Using statistical methods we analyze the correlation about antiepileptic drug-induced mild cutaneous adverse reaction and HLA gene type,and further study the clinical characteristics of antiepileptic drugs-induced mild cutaneous adverse reaction.Results:(1)Maculopapule eruption is the most commom type of antiepileptic drugs-induced cutaneous adverse reaction.(2)Comparison of the experimental group and control group in the HLA classification: There was 1 kind of HLA-A allele and 7 kinds of HLA-B alleles with the OR value greater than 2,they were A*0301,B*1301,B*1501,B*1511,B*3701,B*4002,B*4601 and B*6701;There were 3 alleles of HLA-A and 13 alleles of HLA-B with the OR value less than 0.5,they were 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 and B*5201.Fisher’s exact test was used to calculate the P-values,while the association between these HLA alleles did not reach statistical significance(P>0.05).(3)Comparison of aromatic antiepileptic drugs-induced maculopapule eruption and control group in HLA classification: There were 2 kinds of HLA-A alleles and 2 kinds of HLAB alleles with the OR value greater than 2,they were A*0201,A*3101,B*1301 and B*6701;5 kinds of HLA-B alleles and 10 kinds of HLA-B alleles with the OR value less than 0.5,they were 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.Fisher’s exact test was used to calculate the P-values,while the association between these HLA alleles did not reach statistical significance(P>0.05).(4)Comparison of OXC-induced maculopapule eruption with tolerant group in HLA classification: There were 2 kinds of HLA-A alleles and 5 kinds of HLA-B alleles with the OR value greater than 2,they were A*0201,A*3101,B*1501B*5801,B*6701,B*4002 and B*4601.5 kinds of HLA-B alleles and 11 kinds of HLA-B alleles with the OR value less than 0.5,they were 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 and B*4403.Fisher’s exact test was used to calculate the P-values,while the association between these HLA alleles did not reach statistical significance(P>0.05).(5)Comparison of CBZ-induced maculopapule eruption with tolerant group in HLA classification: There were 4 kinds of HLA-A alleles and 6 kinds of HLA-B alleles with the OR value greater than 2,they were A*0101,A*0201,A*3101,A*6801,B*1301,B*1512,B*3505,B*5601,B*5701 and B*3701.5 kinds of HLA-B alleles and 7 kinds of HLA-B alleles with the OR value less than 0.5,they were A*0207,A*2403,A*3201,A*3303,A*0206,B*1501,B*1518,B*3501,B*4006,B*4402,B*5201 and B*5801.Fisher’s exact test was used to calculate the P-values,while the association between these HLA alleles did not reach statistical significance(P>0.05).(6)Comparison of LEV-induced maculopapule eruption with tolerant group in HLA classification:There were 2 kinds of HLA-A alleles and 5 kinds of HLA-B alleles with the OR value less than 0.5,they were A*0201,A*3101,B*1505,B*3501,B*4001,B*5401 and B*1302.Fisher’s exact test was used to calculate the P-values,while the association between these HLA alleles did not reach statistical significance(P>0.05).(7)Comparison within the experimental group accompanied or not accompanied with itch in HLA classification: There were 3 kinds of HLA-A alleles and 2 kinds of HLA-B alleles with the OR value greater than 2,they were A*0101,A*2402,A*3101,B*1301 and B*3701;3 kinds of HLA-A alleles and 4 kinds of HLA-B alleles with the OR value less than 0.5,they were A*0203,A*1101,A*3001,B*3901,B*4001,B*5201 and B* 5401.Fisher’s exact test was used to calculate the P-values,while the association between these HLA alleles did not reach statistical significance(P>0.05).Conclusion:Antiepileptic drugs-induced mild cutaneous adverse reactions is not significantly associated with HLA gene polymorphism.