Respiratory Epidemiology and Public Health, Imperial College, London, United Kingdom.
J Allergy Clin Immunol. 2011 Nov;128(5):996-1005. doi: 10.1016/j.jaci.2011.08.030.
Hay fever or seasonal allergic rhinitis (AR) is a chronic disorder associated with IgE sensitization to grass. The underlying genetic variants have not been studied comprehensively. There is overwhelming evidence that those who have older siblings have less AR, although the mechanism for this remains unclear.
We sought to identify common genetic variant associations with prevalent AR and grass sensitization using existing genome-wide association study (GWAS) data and to determine whether genetic variants modify the protective effect of older siblings.
Approximately 2.2 million genotyped or imputed single nucleotide polymorphisms were investigated in 4 large European adult cohorts for AR (3,933 self-reported cases vs 8,965 control subjects) and grass sensitization (2,315 cases vs 10,032 control subjects).
Three loci reached genome-wide significance for either phenotype. The HLA variant rs7775228, which cis-regulates HLA-DRB4, was strongly associated with grass sensitization and weakly with AR (P(grass) = 1.6 × 10(-9); P(AR) = 8.0 × 10(-3)). Variants in a locus near chromosome 11 open reading frame 30 (C11orf30) and leucine-rich repeat containing 32 (LRRC32), which was previously associated with atopic dermatitis and eczema, were also strongly associated with both phenotypes (rs2155219; P(grass) = 9.4 × 10(-9); P(AR) = 3.8 × 10(-8)). The third genome-wide significant variant was rs17513503 (P(grass) = 1.2 × 10(-8); PAR = 7.4 × 10(-7)) which was located near transmembrane protein 232 (TMEM232) and solute carrier family 25, member 46 (SLC25A46). Twelve further loci with suggestive associations were also identified. Using a candidate gene approach, where we considered variants within 164 genes previously thought to be important, we found variants in 3 further genes that may be of interest: thymic stromal lymphopoietin (TSLP), Toll-like receptor 6 (TLR6) and nucleotide-binding oligomerization domain containing 1 (NOD1/CARD4). We found no evidence for variants that modified the effect of birth order on either phenotype.
This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses.
花粉症或季节性过敏性鼻炎（AR）是一种与草过敏相关的慢性疾病，与 IgE 致敏有关。潜在的遗传变异尚未得到全面研究。有大量证据表明，那些有兄弟姐妹的人患 AR 较少，尽管其机制尚不清楚。
我们试图利用现有的全基因组关联研究（GWAS）数据，确定与普遍存在的 AR 和草过敏相关的常见遗传变异关联，并确定遗传变异是否会改变兄弟姐妹的保护作用。
在 4 个大型欧洲成人队列中，对大约 220 万个已基因分型或推断的单核苷酸多态性进行了研究，用于 AR（3933 例自述病例与 8965 例对照）和草过敏（2315 例病例与 10032 例对照）。
有 3 个位点在这两种表型上均达到全基因组显著水平。HLA 变体 rs7775228 与草过敏强烈相关，与 AR 弱相关（P(grass) = 1.6×10(-9)；P(AR) = 8.0×10(-3)）。位于染色体 11 开放阅读框 30（C11orf30）和富含亮氨酸重复序列 32（LRRC32）附近的变异也与这两种表型强烈相关（rs2155219；P(grass) = 9.4×10(-9)；P(AR) = 3.8×10(-8)）。第三个全基因组显著变异是 rs17513503（P(grass) = 1.2×10(-8)；P(AR) = 7.4×10(-7)），位于跨膜蛋白 232（TMEM232）和溶质载体家族 25，成员 46（SLC25A46）附近。还确定了 12 个具有提示性关联的其他位点。使用候选基因方法，考虑先前认为重要的 164 个基因内的变异，我们在 3 个进一步的基因中发现了可能有趣的变异：胸腺基质淋巴细胞生成素（TSLP）、Toll 样受体 6（TLR6）和核苷酸结合寡聚化结构域包含蛋白 1（NOD1/CARD4）。我们没有发现变异可以改变出生顺序对这两种表型的影响。
这项对 GWAS 的相对较大的荟萃分析确定了少数与 AR 和草过敏相关的位点。在目前的分析中，没有发现出生顺序的相互作用。
