Association of Vitamin D Binding Protein Variants with Chronic Mucus Hypersecretion in Iceland

Abstract

The results demonstrate similar allele and genotype frequencies of GC in COPD patients overall and healthy controls. However, there was a higher prevalence of genotypes carrying a GC*1F allele and lower prevalence of genotypes with a GC*2 allele in the CMH patients than in controls. This difference was most notable in the homozygous form: 8.3% vs 1.1% for the GC*1F/*1F, and 0.0% vs 7.6% for the GC*2/*2 genotypes, respectively. When controlled for smoking, only the non-smoking CMH patients demonstrated a significantly altered frequency of the GC*1F/*1F genotype (p = 0.0001). The prevalence of the GC*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 the GC*1F and GC*2 alleles are associated with sputum hypersecretion in individuals who are at increased risk of developing COPD.

Vitamin D-binding protein gene polymorphisms and chronic obstructive pulmonary disease susceptibility: A meta-analysis

“…These findings on the correlation between GC polymorphisms and COPD were indirectly supported by the evidence that the VDBP gene influenced vitamin D concentrations and was associated to forced expiratory volume in one second (7,24). However, the results from the present analyses failed to reveal the significant association between the GC polymorphisms and COPD susceptibility among Caucasians, this was extremely different from the findings by Horne et al (32) and Schellenberg et al (23), but consistent with the findings by other studies (21,25,31,33). This may be due to the fact that other factors, such as the differences in age, gender, lifestyle factors, clinical characteristics or the analysis method of the VDBP genotype may have influenced the results.…”

“…1). As for ethnicity, seven studies investigated the Caucasian population (21,(23)(24)(25)31,32) and five studies investigated the Asian population (9,10,19,20,22). The qualities of these studies were considered accessible for the meta-analysis.…”

“…GC*1F, GC*1S and GC*2 are not alleles as such, but haplotypes composed of combinations of the SNPs at these loci, so an individual may be homozygous or heterozygous for each variant, depending on the two haplotypes present. The role of GC polymorphisms in COPD has been explored in a number of studies by investigating the association of GC variants and susceptibility of COPD (9,10,(19)(20)(21)(22)(23)(24)(25). However, the results of these studies were inconclusive and may not be powerful enough due to the limited sample size.…”

Dual role of vitamin D-binding protein 1F allele in chronic obstructive pulmonary disease susceptibility: a meta-analysis

“…However, the 1F allele confers a lower, but not significant risk for COPD compared to the 1S and 2 alleles in Caucasians. However, Laufs et al (2004) reported that the 1F allele is associated with sputum hypersecretion in a Caucasian population at an increased risk for COPD. The limited sample size (48 cases) may explain the different results, and based on the present meta-analysis, the 1F allele may be a protective factor for COPD in Caucasians, although this should be validated in additional studies.…”

“…Horne et al (1990) first reported that GC gene polymorphisms are associated with chronic bronchitis and emphysema in Caucasians. Associations between GC gene polymorphisms and chronic obstructive pulmonary disorder (COPD) have been established over the past decade (Ishii et al, 2001;Laufs et al, 2004;Ito et al, 2004;Lu et al, 2004;Korytina et al, 2006;Shen et al, 2010). However, the GC gene was not identified as a candidate gene for COPD in recent genome-wide association studies (GWAS) (Artigas et al, 2012).…”