Abstract
Background: Iron responsive element binding protein 2 (IREB2) variants may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Recently, many studies have been performed on IREB2 susceptibility variants, including rs2568494, rs2656069, rs10851906, rs12593229, and rs13180, associated with COPD. However, inconsistent findings have been reported. The aim of our research was to determine the association of IREB2 SNPs with COPD.Methods: A comprehensive meta-analysis was performed to accurately estimate the association between IREB2 variants and COPD among four different genetic models.Results: This meta-analysis included a total of 4,096 patients and 5,870 controls. Here, we investigated the 5 IREB2 variants to identify COPD risk. Our results indicate that rs2568494 was associated with an increased risk of COPD for the dominant model (AA+GA vs. GG: OR = 1.150, 95% CI: 1.5–1.304, P = 0.029); rs2656069 was associated with a decreased risk of COPD for the recessive model (GG vs. AA+AG: OR = 0.589, 95% CI: 0.440–0.789; P = 0.000), additive model (GG vs. AA: OR =0.641, 95% CI: 0.441–0.931; P = 0.020), and allele model (G vs. A: OR = 0.812, 95% CI: 0.668–0.988; P = 0.037); and rs10851906 was associated with a decreased risk of COPD for the recessive model (GG vs. AA+AG: OR = 0.732, 95% CI: 0.560–0.958; P = 0.023) and additive model (GG vs. AA: OR = 0.777, 95% CI: 0.637–0.947; P = 0.012).Conclusion: Our findings suggest that the IREB2 rs2568494 minor alleles A may be a genetic factor in susceptibility to COPD. In addition, the minor alleles G of rs2656069 and rs10851906 appear to have a protective effect.
Highlights
Chronic obstructive pulmonary disease (COPD) is a complex human genetic disease characterized by pulmonary dysfunction and incomplete reversibility of airflow obstruction (Rabe et al, 2007)
The severity of airflow limitation was classified according to the GOLD standard (Global Initiative for Chronic Obstructive Lung Disease) as follows: IImoderate, III-severe, and IV-very severe; (4) The control subjects were in Hardy-Weinberg equilibrium (HWE); (5) The selected studies provided SNP genotype amounts or sufficient data for calculation; and (6) The selected studies provided an odds ratio (OR) with a 95% confidence interval (CI) or sufficient data for calculation (He et al, 2015)
The results showed that Iron responsive element binding protein 2 (IREB2) rs2568494 was associated with COPD susceptibility
Summary
Chronic obstructive pulmonary disease (COPD) is a complex human genetic disease characterized by pulmonary dysfunction and incomplete reversibility of airflow obstruction (Rabe et al, 2007). It is predicted to become the fourth leading cause of death by 2030 (Mathers and Loncar, 2006) It is well-known that COPD is the result of interactions between genetic susceptibility and IREB2 Variants and COPD Susceptibility environmental factors. Smoking is an important environmental factor in COPD, the COPD susceptibility of smokers varies, and the disease can appear in non-smokers These results suggest that genetic factors may be among the reasons for individual susceptibility. The study reported that three IREB2 SNPs were associated with COPD patients, and increased expression levels of IREB2 mRNA have been detected in the lungs of smokers and COPD patients (DeMeo et al, 2009), which showed IREB2 as a COPD susceptibility gene. The aim of our research was to determine the association of IREB2 SNPs with COPD
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