SUMF1 Common Variant rs793391 Is Associated with Response to Inhaled Corticosteroids in Patients with COPD - Ntenti, C.; Papakonstantinou, E.; Grize, L.; Pascarella, M.; Frye, B. C.; Fahndrich, S.; Ioannidou, D.; Savic Prince, S.; Goulas, A.; Stolz, D. (Int J Mol Sci, 2025)
This study investigated whether specific sulfatase modifying factor-1 (SUMF1) SNPs-previously linked to lung function-are associated with COPD progression and response to inhaled corticosteroid (ICS) treatment, specifically budesonide, given that SUMF1 expression is altered in COPD and its variants linked to increased disease risk. A subgroup of 165 COPD patients from the HISTORIC study were genotyped for two common SUMF1 SNPs, rs11915920 and rs793391. Patients first underwent a six-week run-in phase with open-label triple inhaled therapy (LAMA/LABA/ICS), then were randomized to receive either LAMA/LABA/placebo or LAMA/LABA/ICS for 12 months. Associations between SNPs, baseline characteristics, and response to ICS-based on FEV(1) change over 12 months-were evaluated. Heterozygotes (TG) for the rs793391 polymorphism treated with LAMA/LABA/ICS showed a significant and clinically meaningful FEV(1) improvement compared to the placebo group. This was supported by improved patient-reported outcomes, with lower SGRQ and CAT scores and a clinically relevant increase in General Health Questionnaire scores. These findings suggest that rs793391 may be linked to both COPD progression and ICS response and could contribute to more personalized treatment strategies in COPD.
Keywords: journalArticle; *Adrenal Cortex Hormones/administration & dosage/therapeutic use; *Polymorphism, Single Nucleotide; *Pulmonary Disease, Chronic Obstructive/drug therapy/genetics; Administration, Inhalation; Aged; Budesonide/therapeutic use/administration & dosage; COPD pharmacogenetics; Female; Humans; Male; Middle Aged; Treatment Outcome; inhaled corticosteroids; personalized therapy; precision medicine; single nucleotide polymorphism; sulfatase modifying factor 1; sulfatases