BackgroundPrevious studies of vitamin D binding protein (VDBP, also known as group-specific component, Gc, encoded by theGCgene) have implicated two gene variants,GC*2 andGC*1F, as possible contributors with chronic obstructive pulmonary disease (COPD) protection and susceptibility, respectively. The objective of this study was to examine the association of VDBP to different subtypes of COPD.Study designThe association of the variousGCgenotypes to the COPD phenotype was examined in Icelandic COPD patients who were followed by pulmonary physicians at the University Hospital of Iceland.MethodsAll patients were genotyped for the known alleles of theGCgene. The single nucleotide polymorphisms (SNPs) were identified by a restriction fragment length polymorphism procedure. Study power was estimated based on allele frequencies of the variants, and risk ratios were calculated from the prevalence of genotypes in the affected group divided by its prevalence in the control population. Statistical analyses were performed using the 2-tailed Fisher’s Exact Test and χ2test, where appropriate.Patient groupOne hundred and two COPD patients and 183 controls, together with 46 asthma patients and 48 patients with chronic mucous hypersecretion (CMH) were examined.Main outcome measure and resultsThe results demonstrate similar allele and genotype frequencies ofGCin COPD patients overall and healthy controls. However, there was a higher prevalence of genotypes carrying aGC*1F allele and lower prevalence of genotypes with aGC*2 allele in the CMH patients than in controls. This difference was most notable in the homozygous form: 8.3% vs 1.1% for theGC*1F/*1F, and 0.0% vs 7.6% for theGC*2/*2 genotypes, respectively. When controlled for smoking, only the non-smoking CMH patients demonstrated a significantly altered frequency of theGC*1F/*1F genotype (p = 0.0001). The prevalence of theGC*2/*2 genotype was also significantly lower in patients with bronchial hypersecretion with airflow obstruction compared with the control group (2.9% vs 7.6%). Taken together, these results demonstrate that theGC*1F andGC*2 alleles are associated with sputum hypersecretion in individuals who are at increased risk of developing COPD.