Ishiyama Yumi, Matsumoto Hisako, Sunadome Hironobu, Tohda Yuji, Horiguchi Takahiko, Kita Hideo, Kuwabara Kazunobu, Tomii Keisuke, Otsuka Kojiro, Fujimura Masaki, Ohkura Noriyuki, Tomita Katsuyuki, Yokoyama Akihito, Ohnishi Hiroshi, Nakano Yasutaka, Oguma Tetsuya, Hozawa Soichiro, Kanemitsu Yoshihiro, Nagasaki Tadao, Ito Isao, Oguma Tsuyoshi, Inoue Hideki, Tajiri Tomoko, Iwata Toshiyuki, Ono Junya, Ohta Shoichiro, Hirota Tomomitsu, Tamari Mayumi, Niimi Akio, Izuhara Kenji, Mishima Michiaki, Hirai Toyohiro
Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine, Osaka, Japan.
J Allergy Clin Immunol Glob. 2025 Jun 10;4(3):100511. doi: 10.1016/j.jacig.2025.100511. eCollection 2025 Aug.
The genetic factors contributing to exacerbations in type 2-low asthma are not well understood.
We sought to clarify the association between variants in gasdermin B/orosomucoid-like 3 () on 17q21 and exacerbations in type 2-low asthma.
This follow-up study of the multicenter Kinki Hokuriku Airway disease Conference (KiHAC) enrolled adults with asthma who were receiving inhaled corticosteroids. It examined associations between asthma exacerbations requiring systemic corticosteroids over 2 years and clinical and genetic factors in patients with the type 2-low endo-genotype, defined by serum periostin levels lower than 95 ng/mL and the rs8832 A allele. Exacerbation risks were also evaluated in patients with the type 2-low genotype, defined by both the rs3829365 C allele and the rs8832 A allele, using the KiHAC and replication cohorts. The genetic variant rs7216389 in was the primary focus for assessing genetic risk.
A total of 115 patients with the type 2-low endo-genotype were analyzed (mean age, 62 years; 76.5% female). During the 2-year follow-up, 32 patients experienced 1 or more exacerbation. Multivariate analysis identified the rs7216389 TT genotype, recent exacerbations, female sex, and higher body mass index as independent risk factors for asthma exacerbations in patients with the type 2-low endo-genotype. The association between the rs7216389 TT genotype and exacerbations was confirmed in patients with the type 2-low genotype in the KiHAC (n = 89) and replication (n = 125) cohorts.
The rs7216389 TT variant on 17q21 may be an independent risk factor for exacerbations in adults with type 2-low asthma, highlighting the role of in its pathophysiology.
导致2型低哮喘加重的遗传因素尚不清楚。
我们试图阐明17号染色体长臂21区（17q21）上gasdermin B/类orosomucoid 3（）基因变异与2型低哮喘加重之间的关联。
这项多中心近畿北陆气道疾病会议（KiHAC）的随访研究纳入了正在接受吸入性糖皮质激素治疗的成年哮喘患者。研究考察了血清骨膜蛋白水平低于95 ng/mL和rs8832 A等位基因所定义的2型低内基因型患者在2年期间需要全身使用糖皮质激素的哮喘加重情况与临床及遗传因素之间的关联。还利用KiHAC和重复队列对由rs3829365 C等位基因和rs8832 A等位基因共同定义的2型低基因型患者的加重风险进行了评估。基因变异rs7216389是评估遗传风险的主要关注点。
共分析了115例2型低内基因型患者（平均年龄62岁；76.5%为女性）。在2年的随访期间，32例患者经历了1次或更多次加重。多变量分析确定rs7216389 TT基因型、近期加重、女性性别和较高的体重指数是2型低内基因型患者哮喘加重的独立危险因素。rs7216389 TT基因型与加重之间的关联在KiHAC队列（n = 89）和重复队列（n = 125）的2型低基因型患者中得到了证实。
17q21上的rs7216389 TT变异可能是2型低哮喘成年患者加重的独立危险因素，突出了在其病理生理学中的作用。
