人类 、 和 基因的多态性与 NSAID 加重的呼吸道疾病的发病风险增加相关。
Polymorphisms in Human , , and Genes Are Associated with an Increased Risk of Developing NSAID-Exacerbated Respiratory Disease.
机构信息
Department of Clinical Biochemistry, University Hospital of Salamanca, 37007 Salamanca, Spain.
Biomedical Research Institute of Salamanca IBSAL, 37007 Salamanca, Spain.
出版信息
Genes (Basel). 2022 Mar 28;13(4):605. doi: 10.3390/genes13040605.
BACKGROUND
The role of genetics in non-steroidal anti-inflammatory drugs (NSAID) exacerbated respiratory disease (NERD) is unclear, with different candidates involved, such as genes, genes related to leukotriene synthesis, and cytokine genes. This study aimed to determine possible associations between 22 polymorphisms in 13 cytokine genes.
METHODS
We included 195 patients (85 with NERD and 110 with respiratory disease who tolerate NSAIDs) and 156 controls (non-atopic individuals without a history of asthma, nasal polyposis (NP), or NSAID hypersensitivity). Genotyping was performed by sequence-specific primer polymerase chain reaction (PCR-SSP). Amplicons were analyzed by horizontal gel electrophoresis in 2% agarose.
RESULTS
Significant differences in allele and genotype frequency distributions were found in (rs1800629), (rs2243248 and rs2243250), and (rs1800896, rs1800871, and rs1800872) genes in patients with NSAID hypersensitivity. In all cases, the minor allele and the heterozygous genotype were more prevalent in NERD. An association of rs1800629 SNP with respiratory disease in NSAID-tolerant patients was also found.
CONCLUSIONS
Retrospectively recorded, we found strong associations of NERD with polymorphisms in , , and genes, suggesting that these genes could be involved in the inflammatory mechanisms underlying NERD.
背景
遗传学在非甾体抗炎药（NSAID）加重的呼吸道疾病（NERD）中的作用尚不清楚，涉及不同的候选基因，如基因、与白三烯合成相关的基因和细胞因子基因。本研究旨在确定 13 个细胞因子基因中的 22 个多态性之间可能存在的关联。
方法
我们纳入了 195 名患者（85 名 NERD 患者和 110 名耐受 NSAID 的呼吸道疾病患者）和 156 名对照（非特应性个体，无哮喘、鼻息肉（NP）或 NSAID 过敏史）。采用序列特异性引物聚合酶链反应（PCR-SSP）进行基因分型。通过 2%琼脂糖水平凝胶电泳分析扩增子。
结果
在 NSAID 过敏患者中， （rs1800629）、 （rs2243248 和 rs2243250）和 （rs1800896、rs1800871 和 rs1800872）基因的等位基因和基因型频率分布存在显著差异。在所有情况下，NERD 中较少的等位基因和杂合基因型更为常见。还发现 rs1800629 SNP 与 NSAID 耐受患者的呼吸道疾病有关。
结论
我们发现 NERD 与 、 、 和 基因中的多态性存在强烈关联，提示这些基因可能参与 NERD 的炎症机制。
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