DNA and Cell Biology, 2019. 38(1), 76-84, DOI: https://doi.org/10.1089/dna.2018.4433

Association of Genetic Variants of NLRP4 with Exacerbation of Asthma: The Effect of Smoking

Soo-Taek Uh, Jong-Sook Park;So-My Koo;Yang-Ki Kim;Ki Up Kim;Mi-Ae Kim;Seung-Woo Shin;Ji-Hye Son;Heung-Woo Park;Hyoung Doo Shin;Choon-Sik Park;Hun Soo Chang

Abstract

Asthma exacerbation is induced by the interaction of genes and environmental factors such as cigarette smoke.NLRP4 counteracts the activity of the inflammasome, which is responsible for asthma exacerbation. In thisstudy, we analyzed the association of single-nucleotide polymorphisms of NLRP4 with the annual rate ofexacerbation and evaluated the additive effect of smoking in 1454 asthmatics. Asthmatics possessing the minorallele of rs1696718G > A had more frequent exacerbation episodes than those homozygous for the commonallele (0.59 vs. 0.36/year) and the association was present only in current and ex-smokers. There was asignificant interaction between the amount smoked and rs16986718 genotypes ( p = 0.014) and a positivecorrelation between the number of annual exacerbation episodes and amount smoked only in rs16986718G > AAA homozygotes. The prevalence of frequent exacerbators (‡2 exacerbation episodes/year) was 2.5 times higherin rs16986718G > A minor allele homozygotes than in common allele homozygotes (12.0% vs. 5.9%). Furthermore,the prevalence was 6 times higher in rs16986718G > A minor allele homozygotes who were currentand ex-smokers than in nonsmokers (25.6% vs. 4.1%). The minor allele of rs16986718G > A in NLRP4 may bea genetic marker that predicts asthma exacerbation in adult asthmatics who smoke.

• DOI: https://doi.org/10.1089/dna.2018.4433
• ISBN or ISSN: 1044-5498

• 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
• This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.