HLA-DRB108:03:02和HLA-DQB106:01:01与中国受试者中对屋尘螨敏感的过敏性鼻炎相关。

HLA-DRB108:03:02 and HLA-DQB106:01:01 are associated with house dust mite-sensitive allergic rhinitis in Chinese subjects.

作者信息

Zhao Yanming, Zhao Yali, Li Jingyun, Zhang Yuan, Zhang Luo

机构信息

Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.

出版信息

Int Forum Allergy Rhinol. 2016 Aug;6(8):854-61. doi: 10.1002/alr.21747. Epub 2016 Mar 25.

DOI:10.1002/alr.21747

PMID:27013183

Abstract

BACKGROUND

Allergic rhinitis (AR) is a multifactorial immunologic disease that is influenced by both genetic and environment factors. House dust mites (HDMs) are important inhalant aeroallergens and are an epidemiologic risk factor for AR. Similarly, the human leukocyte antigen (HLA) class II genes DQB1 and DRB1 have been shown to be associated with AR and play an important role in the regulation of the immune response. The objective of this work was to elucidate the HLA-II gene alleles associated with AR in HDM-sensitive Han Chinese subjects.

METHODS

A total of 142 patients with AR and 184 healthy subjects were recruited to this case-control study. Diagnosis of AR was based on medical history, laryngological examination, skin-prick tests, and HMD-specific immunoglobulin E (IgE) assays. Genotyping of HLA-DRB1 and HAL-DQB1 was performed by the polymerase chain reaction sequence-based genotyping method.

RESULTS

A total of 35 alleles of the HLA-DRB1 locus and 19 alleles of the HLA-DQB1 locus were genotyped in the entire study cohort; the frequencies of alleles DQB106:01:01 (corrected p value [pc ] = 0.009; odds ratio [OR] = 2.684; 95% confidence interval [CI] = 1.482 to 4.994) and DRB108:03:02 (pc = 0.009; OR = 3.754; 95% CI = 1.724 to 8.851) were significantly increased in HDM-sensitive AR patients compared to healthy controls and are considered to be a risk factor for AR in Chinese Han subjects. The frequency of haplotype DRB108:03-DQB106:01 in the HDM-sensitive AR group was also significantly higher than in the control group (9.5% vs 2.4%; pc = 0.005; OR = 4.182; 95% CI = 1.870 to 10.285). Serological antigen types assessment further demonstrated the frequency of HLA-DRB108 (pc = 0.022; OR = 2.982; 95% CI = 1.46 to 6.400) to be significantly increased in HDM-sensitive AR patients, and the frequencies of DRB114 (pc = 0.030; OR = 0.340; 95% CI = 0.154 to 0.694) and DQB105 (pc = 0.030; OR = 0.459; 95% CI = 0.269 to 0.764) to be significantly decreased, compared to healthy controls, suggesting that HLA-DRB108 might be a risk factor, and DRB114 and DQB105 protective factors for HDM-sensitive AR.

CONCLUSION

HLA-DRB108:03:02 and HLA-DQB106:01:01 are associated with HMD-sensitive AR and may confer a risk for development of AR in Han Chinese subjects sensitized to HDM.

摘要

背景

变应性鼻炎（AR）是一种受遗传和环境因素影响的多因素免疫性疾病。屋尘螨（HDM）是重要的吸入性气传变应原，也是AR的一个流行病学危险因素。同样，人类白细胞抗原（HLA）Ⅱ类基因DQB1和DRB1已被证明与AR相关，并在免疫反应调节中起重要作用。这项研究的目的是阐明在对HDM敏感的汉族受试者中与AR相关的HLA -Ⅱ类基因等位基因。

方法

总共142例AR患者和184名健康受试者被纳入这项病例对照研究。AR的诊断基于病史、喉镜检查、皮肤点刺试验和HDM特异性免疫球蛋白E（IgE）检测。采用基于聚合酶链反应序列的基因分型方法对HLA - DRB1和HAL - DQB1进行基因分型。

结果

在整个研究队列中，对HLA - DRB1基因座的35个等位基因和HLA - DQB1基因座的19个等位基因进行了基因分型；与健康对照相比，HDM敏感的AR患者中，等位基因DQB106:01:01（校正P值[pc]=0.009；优势比[OR]=2.684；95%置信区间[CI]=1.482至4.994）和DRB108:03:02（pc = 0.009；OR = 3.754；95% CI = 1.724至8.851）的频率显著增加，被认为是中国汉族受试者AR的一个危险因素。HDM敏感的AR组中，单倍型DRB108:03 - DQB106:01的频率也显著高于对照组（9.5%对2.4%；pc = 0.005；OR = 4.182；95% CI = 1.870至10.285）。血清学抗原类型评估进一步表明，与健康对照相比，HDM敏感的AR患者中HLA - DRB108的频率显著增加（pc = 0.022；OR = 2.982；95% CI = 1.46至6.400），而DRB114（pc = 0.030；OR = 0.340；95% CI = 0.154至0.694）和DQB105（pc = 0.030；OR = 0.459；95% CI = 0.269至0.764）的频率显著降低，这表明HLA - DRB108可能是一个危险因素，而DRB114和DQB105是HDM敏感AR的保护因素。