Single nucleotide polymorphisms (SNPs) in Sulfatase modifying factor (SUMF)-1 are associated with lung function and COPD

Abstract

Single nucleotide polymorphisms (SNPs) in various genes have been shown to associate with chronic obstructive pulmonary disease (COPD), suggesting a role in disease pathogenesis. Sulfatase modifying factor (SUMF1) is a key modifier in connective tissue remodeling, and we have previously shown that several SNPs in SUMF1 are associated with COPD. The aim of this study was to investigate the association between SUMF1 SNPs and advanced lung function characteristics.

Never, former and current smokers with (n=154) or without (n=405) COPD were genotyped for 21 SNPs in SUMF1 and performed spirometry, body plethysmography, diffusing capacity of carbon dioxide (D_LCO) and impulse oscillometry.

Four SNPs (rs793391, rs12634248, rs2819590 and rs304092) showed a significantly decreased odds ratio of having COPD when heterozygous for the variance allele, together with a lower forced expiratory volume in one second (FEV₁)/forced vital capacity (FVC) ratio and FEV₁ and an impaired peripheral resistance and reactance. Moreover, individuals homozygous for the variance allele of rs3864051 exhibited a strong association to COPD, a lower FEV₁/FVC, FEV₁ and D_LCO, and an impaired peripheral resistance and reactance. Other SNPs (rs4685744, rs2819562, rs2819561 and rs11915920) were instead associated with impaired lung volumes and exhibited a lower FVC, total lung capacity (TLC) and alveolar volume (V_A), if having the variance allele.

Several SNPs in the SUMF1 gene are shown to be associated with COPD and impaired lung function. These genetic variants of SUMF1 may cause a deficient sulfation balance in the extracellular matrix of the lung tissue and thereby contributing to the development of COPD.