Intro

Sulfatases are critical molecules that modify proteoglycan chains through the removal of sulfate groups, thus affecting extracellular matrix (ECM) remodeling.?ll sulfatases are regulated by the SUMF1 gene, several polymorphisms of which have been associated with predisposition to COPD. This finding led us to question whether SUMF1 polymorphisms that affect its mRNA expression, could have an impact on lung function characteristics.

Methods

A total of 165 patients with COPD, GOLD stage B-D, subjects of the HISTORIC study, a randomized, placebo-controlled, double-blind, investigator-initiated trial were enrolled. Two common polymorphisms of the SUMF1  gene, rs793391 and rs11915920, were examined in connection to clinical and functional characteristics of the patients. Genotyping was performed with real-time PCR-TAQMAN SNP Genotyping Assay. 

Results

Heterozygous patients for the rs11915920 SNP are presented with lower values for DLCO (p=0.023), higher values of blood neutrophils (p=0.013), lower level of airway smooth muscle cells in endobronchial biopsies (p=0.015) and higher functional residual capacity (FRC) (p=0.027). The % expiratory reserve volume (ERV %) was lower in homozygous patients for the variance allele (p=0.024).Homozygous patients for the rs793391 variance allele had higher N2-MBW values (p>0.001) and lower blood eosinophils (p=0.050).

Coclusion

These results indicate that both studied polymorphisms are associated with lung function parameters in COPD. As these genetic variants of SUMF1 may cause an impaired sulfation balance in the lung ECM, these SNPs may be associated with COPD phenotypes.