Department of Otorhinolaryngology-Head & Neck Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
Department of Otorhinolaryngology-Head & Neck Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
Cytokine. 2018 Nov;111:162-170. doi: 10.1016/j.cyto.2018.08.022. Epub 2018 Aug 28.
Allergic rhinitis (AR) is one of the most common respiratory diseases in children. It is caused by a combination of genetic and environmental factors. Moderate-to-severe AR decreases the quality of life and social performance in children.
To investigate whether polymorphisms in previously published genome-wide association studies (GWAS) allergic disease loci are associated with childhood AR and the severity of AR symptoms in a Chinese Han population.
A case-control study was conducted in 503 pediatric patients with AR and 393 control Chinese school-aged subjects. AR severity was classified as mild or moderate-to-severe according to the AR and its Impact on Asthma (ARIA) guidelines. Overall, 16 tagged single-nucleotide polymorphisms (tSNPs) of published GWAS associations with allergic diseases were selected. All subjects were genotyped and analyzed for the 16 selected tSNPs using the improved multiplex ligation detection reaction (iMLDR) technique.
Both rs7130588_AG and rs7927894_CT genotypes in EMSY region were associated with a significantly increased risk of AR (1.75-fold and 1.50-fold) compared to the AA and CC genotypes, respectively, specific to moderate-to-severe AR. The difference of rs7130588 genotypes in cases vs. controls was still statistically significant under the additive model after multiple test correction to adjust the false discovery rate (FDR) with an adjusted odds ratio of 1.818 and 95% confidence interval (CI) of 1.240-2.664 (P = 0.0349). The rs7130588_G allele was only associated with a high risk of moderate-to-severe AR (1.85-fold, P = 0.003). The rs2227284_TG genotype at the IL4 locus was significantly associated with a 0.65-fold decreased risk of AR compared to the TT genotype. The protective effect of the rs2227284_G allele was also found in different severity of AR. Haplotype analysis showed a significantly increased AR risk associated with the haplotype G-T-T (rs7130588-rs2155219-rs7927894) and a protective effect with the haplotype C-G-C (rs2243250-rs2227284-s2243290).
The loci in EMSY and IL4 can be considered as a hereditary marker for childhood AR. The rs7130588_G allele seems to predispose only to moderate-to-severe AR, though other mechanisms are also likely to be involved.
变应性鼻炎（AR）是儿童最常见的呼吸道疾病之一。它是由遗传和环境因素共同作用引起的。中重度 AR 会降低儿童的生活质量和社交表现。
研究先前发表的全基因组关联研究（GWAS）过敏病部位点的多态性是否与中国汉族人群儿童 AR 及 AR 症状严重程度相关。
采用病例对照研究，纳入 503 例 AR 患儿和 393 例中国学龄期对照。根据 AR 和哮喘影响（ARIA）指南，将 AR 严重程度分为轻度或中重度。总体上，选择了 16 个已发表的与过敏疾病相关的 GWAS 关联的标记单核苷酸多态性（tSNPs）。所有受试者均采用改良多重连接检测反应（iMLDR）技术对 16 个选定的 tSNPs 进行基因分型和分析。
与 AA 和 CC 基因型相比，EMSY 区域的 rs7130588_AG 和 rs7927894_CT 基因型分别与 AR（1.75 倍和 1.50 倍）显著相关，尤其是中重度 AR。对多测试校正以调整假发现率（FDR）后，病例与对照组之间 rs7130588 基因型的差异仍具有统计学意义，校正优势比为 1.818，95%置信区间为 1.240-2.664（P=0.0349）。rs7130588_G 等位基因仅与中重度 AR 的高风险相关（1.85 倍，P=0.003）。IL4 基因座的 rs2227284_TG 基因型与 TT 基因型相比，AR 风险降低 0.65 倍。rs2227284_G 等位基因的保护作用也存在于不同严重程度的 AR 中。单倍型分析显示，与 G-T-T（rs7130588-rs2155219-rs7927894）相关的单倍型显著增加了 AR 风险，与 C-G-C（rs2243250-rs2227284-s2243290）相关的单倍型具有保护作用。
EMSY 和 IL4 基因座可被视为儿童 AR 的遗传标志物。rs7130588_G 等位基因似乎仅导致中重度 AR，但也可能涉及其他机制。
