Kubbara Aahd, Amundson William H, Herman Adam, Lee Adam M, Bishop Jeffrey R, Kim Hyun Joo
Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep, University of Minnesota, Minneapolis, United States.
Pulmonary and Critical Care Medicine, Regions Hospital, University of Minnesota, St. Paul, Minneapolis, MN, United States.
Heliyon. 2023 Jul 24;9(8):e18573. doi: 10.1016/j.heliyon.2023.e18573. eCollection 2023 Aug.
Genetic variations in Idiopathic Pulmonary Fibrosis (IPF) affect survival and outcomes. Current antifibrotic agents are managed based on the patient's reported side effects, although certain single nucleotide polymorphisms (SNPs) might alter treatment response and survival depending on the antifibrotic administered. This study investigated variations in response and outcomes to pirfenidone based on patients-specific genetic profiles.
Retrospective clinical data were collected from 56 IPF patients and had blood drawn for DNA extraction between 7/2013 and 3/2016, with the last patient followed until 10/2018. Nine SNPs were selected for pharmacogenetic investigation based on prior associations with IPF treatment outcomes or implications for pirfenidone metabolism. Genetic variants were examined in relation to clinical data and treatment outcomes.
Of the 56 patients, 38 were males (67.85%). The average age of IPF at diagnosis was 66.88 years. At the initiation of pirfenidone, the average percent predicted FVC was 70.7%, and the average DLCO percent predicted was 50.02% (IQR 40-61%). Among the genetic variants tested, the TOLLIP rs5743890 risk allele was significantly associated with improved survival, with increasing pirfenidone duration. This finding was observed with CC or CT genotype carriers but not for those with the TT genotype (p = 0.0457). Similarly, the TGF-B1 rs1800470 risk allele was also significantly associated with improved survival with longer pirfenidone therapy (p = 0.0395), even though it was associated with disease progression.
This pilot study suggests that in IPF patients, the TOLLIP rs5743890 genotypes CC and CT, as well as TGF-B1 rs 1800470 may be associated with increased survival when treated with pirfenidone.
特发性肺纤维化（IPF）的基因变异会影响生存率和预后。目前的抗纤维化药物是根据患者报告的副作用来管理的，尽管某些单核苷酸多态性（SNP）可能会根据所使用的抗纤维化药物改变治疗反应和生存率。本研究基于患者特定的基因谱调查了吡非尼酮的反应和预后差异。
回顾性收集了56例IPF患者2013年7月至2016年3月期间的临床数据并采集血样用于DNA提取，最后一名患者随访至2018年10月。基于先前与IPF治疗结果的关联或对吡非尼酮代谢的影响，选择了9个SNP进行药物遗传学研究。研究了基因变异与临床数据和治疗结果的关系。
56例患者中，38例为男性（67.85%）。IPF诊断时的平均年龄为66.88岁。开始使用吡非尼酮时，预测FVC的平均百分比为70.7%，预测DLCO的平均百分比为50.02%（四分位间距40 - 61%）。在所检测的基因变异中，TOLLIP rs5743890风险等位基因与生存率提高显著相关，且随着吡非尼酮使用时间延长而增加。CC或CT基因型携带者有此发现，而TT基因型携带者则无（p = 0.0457）。同样，TGF - B1 rs1800470风险等位基因也与吡非尼酮治疗时间延长后的生存率提高显著相关（p = 0.0395），尽管它与疾病进展有关。
这项初步研究表明，在IPF患者中，TOLLIP rs5743890基因型CC和CT以及TGF - B1 rs1800470在用吡非尼酮治疗时可能与生存率提高有关。
