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TGF-β 信号通路基因 miRNA 靶位多态性与变应性鼻炎易感性。

Polymorphisms in MicroRNA Target Sites of TGF-β Signaling Pathway Genes and Susceptibility to Allergic Rhinitis.

机构信息

Department of Otorhinolaryngology and Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.

Department of Otorhinolaryngology, The Affiliated Changzhou No. 2 People's Hospital, Nanjing Medical University, Changzhou, China.

出版信息

Int Arch Allergy Immunol. 2021;182(5):399-407. doi: 10.1159/000511975. Epub 2021 Feb 17.

Abstract

BACKGROUND

The polymorphisms inside microRNA target sites locating in the 3'-UTR region may introduce the micro-RNA-binding changes, which may regulate the gene expression and correlate with the potential diseases.

OBJECTIVES

We aimed to investigate whether the polymorphisms in microRNA target sites of transforming growth factor beta (TGF-β) signaling pathway genes are associated with the susceptibility of mite-sensitized allergic rhinitis (AR) in a Han Chinese population.

METHODS

In this case-control study, 454 AR patients and 448 healthy controls were recruited. Three HapMap single-nucleotide polymorphisms (SNPs) were mapped to putative microRNA recognition sites and genotyped by TaqMan allelic discrimination assay.

RESULTS

The genotype and allele frequencies of 3 SNPs (rs1590 in TGFBR1; rs1434536 and rs17023107 in BMPR1B) showed lack of significant association with AR. However, in the subgroup analysis, the TG, GG, and TG/GG genotypes of rs1590 exhibited significantly increased risk of AR in the male subgroup (TG: adjusted OR = 1.57, 95% CI = 1.08-2.31; GG: adjusted OR = 1.76, 95% CI = 1.09-2.86; TG/GG: adjusted OR = 1.62, 95% CI = 1.13-2.33). The CT genotypes of rs17023107 might have potential to protect against AR in the patients age of <15 years (adjusted OR = 0.37, 95% CI = 0.14-0.95) and the males (adjusted OR = 0.48, 95% CI = 0.25-0.95). No significant association was found between SNPs and the total serum IgE level.

CONCLUSIONS

In a Han Chinese population, stratified by age and gender, susceptibility to mite-sensitized AR may be associated with 2 SNPs (rs1590 and rs17023107) in microRNA target sites of TGF-β signaling pathway genes.

摘要

背景

位于 3'UTR 区的 microRNA 靶位的多态性可能会导致 microRNA 结合的改变,从而调节基因表达,并与潜在疾病相关。

目的

我们旨在研究转化生长因子β(TGF-β)信号通路基因的 microRNA 靶位多态性是否与汉族螨致敏变应性鼻炎(AR)的易感性相关。

方法

在这项病例对照研究中,共招募了 454 例 AR 患者和 448 例健康对照者。采用 TaqMan 等位基因鉴别检测法对 3 个单核苷酸多态性(SNP)(TGFBR1 中的 rs1590;BMPR1B 中的 rs1434536 和 rs17023107)进行基因分型。

结果

3 个 SNP(rs1590 在 TGFBR1 中;rs1434536 和 rs17023107 在 BMPR1B 中)的基因型和等位基因频率与 AR 无显著相关性。然而,在亚组分析中,rs1590 的 TG、GG 和 TG/GG 基因型在男性亚组中显示出 AR 的显著风险增加(TG:调整 OR = 1.57,95%CI = 1.08-2.31;GG:调整 OR = 1.76,95%CI = 1.09-2.86;TG/GG:调整 OR = 1.62,95%CI = 1.13-2.33)。rs17023107 的 CT 基因型可能有潜力保护<15 岁的患者(调整 OR = 0.37,95%CI = 0.14-0.95)和男性(调整 OR = 0.48,95%CI = 0.25-0.95)免受 AR 的影响。SNP 与总血清 IgE 水平之间无显著相关性。

结论

在汉族人群中,按年龄和性别分层,螨致敏变应性鼻炎的易感性可能与 TGF-β 信号通路基因的 microRNA 靶位的 2 个 SNP(rs1590 和 rs17023107)相关。

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