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Different Associations Between the IREB2 Variants and Chronic Obstructive Pulmonary Disease Susceptibility.

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.

SUBMITTER: Zeng Q

PROVIDER: S-EPMC7701307 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Different Associations Between the IREB2 Variants and Chronic Obstructive Pulmonary Disease Susceptibility.

Zeng Qiaoli Q Chen Qikang Q Zou Dehua D Guo Runmin R Xiao Dawei D Jiang Shaohu S Chen Riling R Wang Yajun Y Ma Guoda G

Frontiers in genetics 20201116

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: ...[more]

PMID: 33304392

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Project description:BackgroundGenetic studies have previously reported that single-nucleotide polymorphisms (SNPs) in CHRNA genes (such as CHRNA3, CHRNA4, CHRNA5, or CHRNA3-CHRNA5-CHRNB4 clusters) are linked to the risk of neoplastic and non-neoplastic diseases. However, these conclusions were controversial and no systematic research synopsis has been available. We aimed to synthesize current knowledge of variants in the CHRNA genes on the risk of diseases.MethodsWe systematically searched for publications using PubMed, Medline, and Web of Science on or before 25 August 2021. A total of 1,818 publications were identified, of which 29 were deemed eligible for inclusion that could be used to perform meta-analysis based on at least three data sources to assess whether the morbidity associated with neoplastic and non-neoplastic diseases can be attributed to SNPs in CHRNA genes. To further evaluate the authenticity of cumulative evidence proving significant associations, the present study covered the Venice criteria and false-positive report probability tests. Through the Encyclopedia of DNA Elements (ENCODE) project, we created functional annotations for strong associations.ResultsMeta-analyses were done for nine genetic variants with two diseases {chronic obstructive pulmonary disease (COPD) and lung cancer (LC)}that had at least three data sources. Interestingly, eight polymorphisms were significantly related to changes in the susceptibility COPD and LC (p < 0.05). Of these, strong evidence was assigned to six variants (28 significant associations): CHRNA3 rs1051730, CHRNA3 rs6495309, and CHRNA5 rs16969968 with COPD risk, and CHRNA3 rs1051730, CHRNA3 rs578776, CHRNA3 rs6495309, CHRNA3 rs938682, CHRNA5 rs16969968, and CHRNA5 rs588765 with LC risk; moderate evidence was assigned to five SNPs (12 total associations) with LC or COPD risk. Data from ENCODE and other public databases showed that SNPs with strong evidence may be located in presumptive functional regions.ConclusionsOur study summarized comprehensive evidence showing that common mutations in CHRNA genes are strongly related to LC and COPD risk. The study also elucidated the vital function of CHRNA genes in genetic predispositions to human diseases.

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Different Associations Between the IREB2 Variants and Chronic Obstructive Pulmonary Disease Susceptibility.

Publications

Different Associations Between the <i>IREB2</i> Variants and Chronic Obstructive Pulmonary Disease Susceptibility.

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