Vitamin D Binding Protein Variants and the Risk of COPD

Abstract

Although the development of chronic obstructive pulmonary disease (COPD) in smokers shows genetic susceptibility, only alpha1-antitrypsin deficiency has been identified as a definite genetic risk factor. There have been three previous studies in which associations between Gc-globulin phenotypes and COPD have been investigated. Although some data suggest an association, the results were inconclusive. Because smoking is the major risk factor for COPD, it may have been a confounding factor in previous studies. We have investigated Gc-globulin genotypic frequencies among 75 COPD patients and 64 nonobstructed controls. Both groups had significant smoking histories: pack-years (mean +/- SD) of 52 +/- 30 and 48 +/- 27, respectively. The results show that homozygosity for the Gc2 allele is protective against COPD (OR = 0.17, 95% CI = 0.03 to 0.83). There were no differences between genotypes for lung elastic recoil values or for the level of upstream airway resistance. Gc-globulin can enhance complement (C5a)-mediated neutrophil chemotaxis. Because neutrophils play a role in parenchymal destruction and airway inflammation, we examined whether Gc-globulin's ability to enhance neutrophil chemotaxis varied with genotype. We found no difference among genotypes with respect to neutrophil chemotaxis suggesting that the protective effect of the Gc2 allele is mediated through a different mechanism.

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.…”

Aberrant fibrillin-1 expression in early emphysematous human lung: a proposed predisposition for emphysema

“…67 However, strong associations between these polymorphisms and the elastic recoil properties of the lung are lacking and correlations with protein levels in human lung have not been reported. 68,69 Our study presents data that correlate fibrillin-1 to the onset of adult emphysema. This, together with the notion that mutations in the fibrillin-1 gene may result in emphysematous lesions in man (Marfan syndrome) as well as mice, makes the fibrillin-1 gene a strong candidate for the predisposition of smokers to emphysema.…”

Exploring Unique Structures: Flexibility is a Significant Factor in Biological Activity

“…Recently, the relationship between the risk of chronic obstructive pulmonary disease (COPD) and the Gc protein allele type, such as Gc*1F, Gc*1S, Gc*2, had been reported. [93][94][95][96][97] Gc*1F increased the COPD risk, while Gc*2 suppressed the risk. Thus, the allele type of Gc protein is an important factor in COPD.…”