Munthe-Kaas M C, Carlsen K L, Carlsen K H, Egeland T, Håland G, Devulapalli C S, Akselsen H, Undlien D
Department of Pediatrics, Ullevål University Hospital, Oslo, Norway.
Allergy. 2007 Sep;62(9):991-8. doi: 10.1111/j.1398-9995.2007.01377.x.
The HLA (human leukocyte antigen) class II genes DQB1 and DRB1 and the Tumor Necrosis Factor alpha gene (TNFA) within the HLA complex (chromosome 6p21) have been associated with asthma and allergy. Due to the strong linkage disequilibrium characterizing this complex and the multiple asthma/allergy expressions, we aimed to determine which of these genes were primarily involved in specific asthma/allergy traits.
The DRB1-DQB1 alleles and TNFA-308 polymorphism were genotyped in 959 children from the Environment and Childhood Asthma study and analyzed for possible associations with allergic and non-allergic asthma (with/without at least one positive skin prick test for allergens) and specific allergic sensitization, as well as bronchial hyperresponsiveness and total IgE, using both allele and extended haplotype analyses.
Different genes within the HLA complex were associated with separate asthma and allergy traits. Nonallergic asthma was associated with both the TNFA-308A allele [Odds ratio (OR) 1.7 (1.3-2.3)] and DRB1 03 allele [OR 1.6(1-2.6)], but extended DRB1 03-TNFA-308 haplotype analysis suggested that the DRB1-DQB1 association was secondary to linkage disequilibrium with the TNFA-308 polymorphism. Allergies were associated with HLA class II alleles only; birch sensitization with DQB1 0603-DRB1 13 [OR 2.3 (1.4-4.0)] and mugwort sensitization with DQB1 0609-DRB1 13 [OR 7.1 (1.9-27.0)] and DQB1 0501-DRB1 01 [OR 2.0 (1.0-4.0)].
Our data suggests that asthma is not associated with DRB1 or DQB1 but rather TNFA or a gene(s) in linkage disequilibrium, while sensitization to specific allergens is associated with particular alleles at the DQ and/or DR loci. A novel association between DQB1 0603-DRB1 13 and birch allergy is identified.
人类白细胞抗原（HLA）Ⅱ类基因DQB1和DRB1以及HLA复合体（6号染色体p21）内的肿瘤坏死因子α基因（TNFA）与哮喘和过敏相关。由于该复合体存在强烈的连锁不平衡以及多种哮喘/过敏表现，我们旨在确定这些基因中哪些主要参与特定的哮喘/过敏特征。
在“环境与儿童哮喘”研究中的959名儿童中对DRB1 - DQB1等位基因和TNFA - 308多态性进行基因分型，并使用等位基因和扩展单倍型分析，分析其与过敏性和非过敏性哮喘（对过敏原至少有一次阳性皮肤点刺试验）、特定过敏致敏、支气管高反应性和总IgE的可能关联。
HLA复合体内的不同基因与不同的哮喘和过敏特征相关。非过敏性哮喘与TNFA - 308A等位基因[比值比（OR）1.7（1.3 - 2.3）]和DRB1 03等位基因[OR 1.6（1 - 2.6）]均相关，但扩展的DRB1 03 - TNFA - 308单倍型分析表明，DRB1 - DQB1关联是与TNFA - 308多态性连锁不平衡的次要结果。过敏仅与HLAⅡ类等位基因相关；桦树致敏与DQB1 0603 - DRB1 13 [OR 2.3（1.4 - 4.0）]相关，艾蒿致敏与DQB1 0609 - DRB1 13 [OR 7.1（1.9 - 27.0）]和DQB1 0501 - DRB1 01 [OR 2.0（1.0 - 4.0）]相关。
我们的数据表明，哮喘与DRB1或DQB1无关，而是与TNFA或处于连锁不平衡的一个或多个基因相关，而对特定过敏原的致敏与DQ和/或DR位点的特定等位基因相关。确定了DQB1 0603 - DRB1 13与桦树过敏之间的新关联。
