Single-nucleotide polymorphisms in the sulfatase-modifying factor 1 gene are associated with lung function and COPD.

Single nucleotide polymorphisms (SNPs) in various genes have been shown to associate with COPD, suggesting a role in disease pathogenesis. Sulfatase modifying factor (SUMF1) is a key modifier in connective tissue remodelling, and we have shown previously that several SNPs in are associated with COPD. The aim of this study was to investigate the association between 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 and underwent spirometry, body plethysmography, diffusing capacity of the lung for carbon monoxide ( ) measurement 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 1 s (FEV) and FEV/forced vital capacity (FVC) ratio and an impaired peripheral resistance and reactance. Moreover, individuals homozygous for the variance allele of rs3864051 exhibited a strong association to COPD, a lower FEV/FVC, FEV and , 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 and alveolar volume, in individuals having the variance allele. Several SNPs in the gene are shown to be associated with COPD and impaired lung function. These genetic variants of may cause a deficient sulfation balance in the extracellular matrix of the lung tissue, thereby contributing to the development of COPD.