人类白细胞抗原Ⅱ类基因多态性与中国人群尘螨过敏性鼻炎相关性研究

Association between human leukocyte antigen Ⅱ(HLA-Ⅱ) gene polymorphism and house dust mites-sensitive allergic rhinitis in Chinese subjects

目的探索人类白细胞抗原Ⅱ类基因(human leukocyte antigenⅡ,HLA-Ⅱ)多态性在中国人群中尘螨过敏性鼻炎发病中的作用。方法选取单纯尘螨过敏性鼻炎(allergic rhinitis,AR)病人71例,健康对照92例,提取受试者外周血DNA,应用聚合酶链反应序列分型法(polymerase chain reaction sequence-based genotyping,PCR-SBT)进行HLA-Ⅱ基因(DRB1、DQB1)分型。采用R软件进行HLA-Ⅱ基因频率统计及单倍体型分析包进行统计学分析,基因频率在AR与对照组中的比较应用χ2及Fisher精确检验分析,结果进行Bonferroni多重矫正。结果共检测到16个HLA-DRB1等位基因,13个HLA-DQB1等位基因。其中DQB1*06:01:01(P校正=0.010,OR=2.347,95%CI:1.392~4.225)、DRB1*08:03:02(P校正=0.012,OR=3.213,95%CI:1.732~7.821),在尘螨过敏性病人中的基因频率较健康对照组增加,差异具有统计学意义。结果提示,HLA-DRB1*08:03:02和HLA-DQB1*06:01:01等位基因可能是中国人群尘螨过敏性鼻炎发病的风险因子。单倍体型DRB1*08:03-DQB1*06:01(19%vs 4.8%,P校正=0.007,OR=4.232,95%CI:1.822~9.237)在病例组中频率增加。结论 HLA-DRB1*08:03:02和HLA-DQB1*06:01:01等位基因可能是中国人群尘螨过敏性鼻炎发病的风险因子。

Objective To elucidate the human leukocyte antigenⅡ（HLA-Ⅱ） gene alleles associated with allergic rhinitis（AR） in house dust mites sensitive（HDM-sensitive） Han Chinese subjects. Methods Seventy-one patients with AR and 92 healthy subjects were recruited to this case control study. Frequencies of HLA were estimated by using the R statistical analysis package. Significance was evaluated using χ2test and Fisher exact test. For multiple allelic frequency comparisons,Bonferroni correction was applied. Genotyping of HLA-DRB1 and HAL-DQB1 was performed by the polymerase chain reaction sequence-based genotyping method. Results A total of 16 alleles of the HLA-DRB1 locus and13 alleles of the HLA-DQB1 locus were genotyped in the entire study cohort; of which the frequencies of alleles DQB1＊ 06： 01： 01（P = 0. 010,OR = 2. 347,95% CI ： 1. 392-4. 225） and DRB1＊ 08： 03： 02（P = 0. 012,OR = 3. 213,95% CI ： 1. 732-7. 821） were significantly increased in HDM-sensitive AR patients compared to healthy controls and considered to be a risk factor for AR in Chinese Han subjects. The frequency of haplotype DRB1＊ 08： 03-DQB1＊ 06： 01 in HDM-sensitive AR group was also significantly higher than that in the control group（19% vs 4. 8%,P = 0. 007,OR = 4. 232; 95% CI ： 1. 822-9. 237）. Conclusion HLA-DRB1＊ 08： 03： 02 and HLA-DQB1＊ 06： 01： 01 are associated with mitessensitive AR and may confer a risk for development of AR in Han Chinese subjects sensitized to HDM.