Association of ATP8B3 gene polymorphisms with aspirin-exacerbated respiratory disease in asthmatics.

IF 1.7 3区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Pharmacogenetics and genomics Pub Date : 2022-10-01 DOI:10.1097/FPC.0000000000000480

Jong-Uk Lee, Min Kyung Kim, Seung-Lee Park, Da Jeong Bae, Hun Soo Chang, Choon-Sik Park, Jong Sook Park

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引用次数: 0

Abstract

Background: Aspirin-exacerbated respiratory disease (AERD), an asthma phenotype, often presents with severe manifestations and it remains widely underdiagnosed because of insufficient awareness of the relationship between the ingestion of nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid (ASA), and asthma exacerbation. Our previous genome-wide association study demonstrated an association between a single nucleotide polymorphism (SNP) of the ATP8B3 gene and the risk of AERD. This study examined AERD-related SNPs of the ATP8B3 gene in a large population.

Methods: Twenty-five SNPs of ATP8B3 were genotyped with the GoldenGate assay using VeraCode microbeads in 141 asthmatics with AERD and 995 Aspirin-tolerant asthma (ATA). The genotype distribution was analyzed using logistic regression models. The declines in forced expiratory volume in 1 second (FEV1)following an ASA challenge were compared among the genotypes and haplotypes using a type III generalized linear model.

Results: The minor allele frequencies (MAFs) of rs10421558 A>G in the 5'UTR and rs10403288 G>A in the intron were significantly lower in the AERD than the ATA [34.0% vs. 43.8%, OR = 0.66 (0.62-0.92), Pcorr = 0.03 and 28.4% vs. 35.4%, OR = 0.62 (0.59-0.89), Pcorr = 0.016, respectively]. BL1ht5 was significantly higher in the AERD [7.6% vs. 1.6%, OR = 12.23 (0.2-0.51), P = 4.7 × 10 -4 , Pcorr = 0.001]. Among them, rs10421558 A>G and BL1ht5 were associated with the percent decline in FEV1 on the oral ASA challenge test.

Conclusion: The minor allele of rs10421558 A>G in the 5'UTR may protect against the development of AERD via the increased production of ATP8B3.

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ATP8B3基因多态性与哮喘患者阿司匹林加重呼吸系统疾病的关系

背景:阿司匹林加重呼吸系统疾病(AERD)是一种哮喘表型，通常表现为严重的症状，由于对摄入非甾体类抗炎药(包括乙酰水杨酸(ASA))与哮喘恶化之间的关系认识不足，该病仍被广泛误诊。我们之前的全基因组关联研究表明，ATP8B3基因的单核苷酸多态性(SNP)与AERD风险之间存在关联。本研究在大量人群中检测了与aerd相关的ATP8B3基因snp。方法:使用VeraCode微珠对141例AERD和995例阿斯匹林耐受性哮喘(ATA)患者的25个ATP8B3 snp进行GoldenGate基因分型。采用logistic回归模型分析基因型分布。使用III型广义线性模型比较了ASA刺激后1秒用力呼气量(FEV1)在基因型和单倍型之间的下降。结果:5'UTR中rs10421558 A>G和内含子中rs10403288 G>A的次要等位基因频率(MAFs)在AERD中显著低于ATA[34.0%比43.8%，OR = 0.66 (0.62-0.92)， Pcorr = 0.03和28.4%比35.4%，OR = 0.62 (0.59-0.89)， Pcorr = 0.016]。BL1ht5在AERD中显著升高[7.6%比1.6%，OR = 12.23 (0.2-0.51)， P = 4.7 × 10 -4, Pcorr = 0.001]。其中rs10421558 A>G和BL1ht5与口服ASA激发试验中FEV1下降百分比相关。结论:5'UTR中rs10421558 A>G的小等位基因可能通过增加ATP8B3的产生来抑制AERD的发生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenetics and genomics 医学-生物工程与应用微生物

CiteScore

3.20

自引率

3.80%

发文量

审稿时长

3 months

期刊介绍： Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.