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  • Title: The association between sixteen genome-wide association studies-related allergic diseases loci and childhood allergic rhinitis in a Chinese Han population.
    Author: Li Y, Chen J, Rui X, Li N, Jiang F, Shen J.
    Journal: Cytokine; 2018 Nov; 111():162-170. PubMed ID: 30170133.
    Abstract:
    BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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 (PFDR = 0.0349). The rs7130588_G allele was only associated with a high risk of moderate-to-severe AR (1.85-fold, Page and gender_adjustment = 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). CONCLUSIONS: 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.
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