Vitamin D binding protein genotype variants and risk of chronic obstructive pulmonary disease: a meta-analysis

Genetic susceptibility for development of chronic obstructive pulmonary disease (COPD) is under intensive investigation. Among the three alleles of vitamin D binding protein, or group-specific (GC) components, some have suggested that having GC-1F and GC-2 alleles was associated with a risk of COPD. Although previous studies have shown considerable variance, no meta-analysis has been conducted.

Through four databases, two independent investigators searched for case-control studies providing sufficient data to calculate odds ratios by the vitamin D binding protein allele variant and genotype variant for a case of COPD. Studies whose control did not satisfy the Hardy-Weinberg equilibrium (Chi-square P ≥ 0.05) were excluded. We used a fixed-model to estimate the pooled odds ratio at both allele and genotype level.

Of 141 candidate studies, six were included. We analysed 1712 subjects, consisting of 466 Asians, 1246 Caucasians, 531 COPD cases and 1181 non-COPD controls. The prevalence of each allele among the 1181 controls was as follows: GC-1F 14.0%, GC-1S 53.8% and GC-2 31.9%. When compared to GC-1S, the GC-1F allele and GC-2 allele were associated with COPD risk with pooled odds ratios of 1.44 (95% CI 1.14-1.83, P = 0.002) and 0.83 (95% CI 0.69-0.996, P = 0.045), respectively. When compared to the 1S-1S genotype, the 1F-1F genotype was a risk factor of COPD with pooled odds ratio of 2.64 (95% CI 1.29-5.39, P = 0.008).

The GC-1F allele of the vitamin D binding protein was a risk for COPD in recessive mode.