芳香族致敏与HLA-B~*1502基因多态性之间的相关性研究
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摘要
目的:遗传医学和预防医学的发展开辟了新的领域,芳香族致敏在身体经酶代谢后与蛋白多肽形成半抗原复合物,可诱发后来的过敏反应,本研究分析HLA-B*1502基因多态性与芳香族致敏发病风险及治疗疗效的关系。方法:选取43例芳香族致敏患者作为试验组,另选取110例同期体检健康者作为对照组,分析HLA-B*1502基因的多态性,采集所有患者空腹静脉血,采用酚-氯仿法从分离出的白细胞中提取脱氧核糖核酸(DNA),采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术分析HLA-B*1502的多态性,并比较其与芳香族致敏的发病风险及其治疗疗效的相关性。结果:通过对HLA-B*1502启动子区单核苷酸多态性的分析发现,经线性回归分析发现,携带CT/TT基因型较其他基因型的患者芳香族致敏发生率明显增高(P<0.05);通过对HLA-B*1502包含的1/1、1/2、1/3、1/4、2/2与4/4基因型的分析发现,以上6种基因型在试验组和对照组的分布差异无统计学意义(P>0.05),由主效应分析可知,变异型基因1/2与2/2可能降低芳香族致敏的发生率,但病例数较少,因此没有统计学意义(P>0.05);HLA-B*1502基因的多态性与芳香族致敏的临床治疗效果无明显相关性(P>0.05)。结论:携带CT/TT基因型的HLA-B*1502可能提高芳香族致敏的发病率,HLA-B*1502基因多态性与芳香族致敏的临床治疗效果不相关。
Objective: The development of genetic medicine and preventive medicine has opened up a new field, aromatic sensitization in the body after the enzyme metabolism and protein polypeptide to form a semi-antigen complex, can induce later allergic reaction, this study analyzed the HLA-B*1502 gene polymorphism and the incidence of aromatic sensitization risk and therapeutic efficacy of the relationship. Methods: 43 cases were selected as the test group, and 110 patients with the same health were selected as the control groups. The polymorphism of HLA-B*1502 gene was analyzed, the fasting venous blood was collected, and the DNA(DNA) was extracted from white cells separated by phenol-chloroform method. The polymorphism of HLA-B*1502 was analyzed by restrictive fragment length polymorphism polymerase chain reaction(PCR-RFLP), and its correlation with the risk of aromatic sensitization and its therapeutic efficacy was compared. Results: According to the analysis of single nucleotide polymorphism in HLA-B*1502 promoter region, it was found that the incidence of aromatic sensitization was significantly higher in patients with ct/tt genotype than in other genotypes(P<0.05); Through the HLA-B*1502 contained 1/1, 1/2, 1/3, 1/4, 2/2 and 4/4 genotype analysis showed that there was no statistically significant difference in the distribution of the above 6 genotypes in the test group and the control groups(P>0.05), and it was found from the main effect analysis that the variable-shaped gene 1/2 and 2/2 could decrease the incidence of aromatic sensitization, but the number of cases was less Therefore, there was no statistically significant(P>0.05), and there was no significant correlation between the polymorphism of HLA-B*1502 gene and the clinical efficacy of aromatic sensitization(P>0.05). Conclusion: The HLA-B*1502 with CT/TT genotype may improve the incidence of aromatic sensitization, and HLA-B*1502 gene polymorphism is not related to the clinical therapeutic effects of aromatic sensitization.
Objective: The development of genetic medicine and preventive medicine has opened up a new field, aromatic sensitization in the body after the enzyme metabolism and protein polypeptide to form a semi-antigen complex, can induce later allergic reaction, this study analyzed the HLA-B*1502 gene polymorphism and the incidence of aromatic sensitization risk and therapeutic efficacy of the relationship. Methods: 43 cases were selected as the test group, and 110 patients with the same health were selected as the control groups. The polymorphism of HLA-B*1502 gene was analyzed, the fasting venous blood was collected, and the DNA(DNA) was extracted from white cells separated by phenol-chloroform method. The polymorphism of HLA-B*1502 was analyzed by restrictive fragment length polymorphism polymerase chain reaction(PCR-RFLP), and its correlation with the risk of aromatic sensitization and its therapeutic efficacy was compared. Results: According to the analysis of single nucleotide polymorphism in HLA-B*1502 promoter region, it was found that the incidence of aromatic sensitization was significantly higher in patients with ct/tt genotype than in other genotypes(P<0.05); Through the HLA-B*1502 contained 1/1, 1/2, 1/3, 1/4, 2/2 and 4/4 genotype analysis showed that there was no statistically significant difference in the distribution of the above 6 genotypes in the test group and the control groups(P>0.05), and it was found from the main effect analysis that the variable-shaped gene 1/2 and 2/2 could decrease the incidence of aromatic sensitization, but the number of cases was less Therefore, there was no statistically significant(P>0.05), and there was no significant correlation between the polymorphism of HLA-B*1502 gene and the clinical efficacy of aromatic sensitization(P>0.05). Conclusion: The HLA-B*1502 with CT/TT genotype may improve the incidence of aromatic sensitization, and HLA-B*1502 gene polymorphism is not related to the clinical therapeutic effects of aromatic sensitization.
引文
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[6]Kim SH,Lee KW,Song WJ,et al.Adverse Drug Reaction Research Group in Korea Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans[J].Epilepsy Res,2011,97(1-2):190-197.
[7]Li LJ,Hu FY,Wu XT,et al.Predictive markers for carbamazepine and lamotrigine-induced maculopapular exanthema in Han Chinese[J].Epilepsy Res,2013,106(1-2):296-300.
[2]Lee KW,Park MH.New HLA nomenclature(2010)and its clinical application in Koreans[J].Korean J Lab Med,2010,30(3):203-217.
[3]Aihara M.Pharmacogenetics of cutaneous adverse drug reactions[J].J Dermatol,2011,38(3):246-254.
[4]Criado PR,Criado RFJ,Avancini JM,et al.Drug reaction with eosinophilia and systemic symptoms(DRESS)/drug-induced hypersensitivity syndrome(DIHS):a review of current concepts[J].An Bras Dermatol,2012,87(3):435-49.
[5]Tangamornsuksan W,Chaiyakunapruk N,Somkrua R,et al.Relationship between the HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis:a systematic review and meta-analysis[J].JAMA Dermatol,2013,149(9):1025-1032.
[6]Kim SH,Lee KW,Song WJ,et al.Adverse Drug Reaction Research Group in Korea Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans[J].Epilepsy Res,2011,97(1-2):190-197.
[7]Li LJ,Hu FY,Wu XT,et al.Predictive markers for carbamazepine and lamotrigine-induced maculopapular exanthema in Han Chinese[J].Epilepsy Res,2013,106(1-2):296-300.