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      International Journal of COPD (submit here)

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      Is Open Access

      CYP2B6 genetic polymorphisms influence chronic obstructive pulmonary disease susceptibility in the Hainan population

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          Abstract

          Introduction

          Chronic obstructive pulmonary disease (COPD) is a lung disease closely related to exposure to exogenous substances. CYP2B6 can activate many exogenous substances, which in turn affect lung cells. The aim of this study was to assess the association of single-nucleotide polymorphisms (SNPs) in CYP2B6 with COPD risk in a Chinese Han population.

          Materials and methods

          Genotypes of the five candidate SNPs in CYP2B6 were identified among 318 cases and 508 healthy controls with an Agena MassARRAY method. The association between CYP2B6 polymorphisms and COPD risk was evaluated using genetic models and haplotype analyses.

          Results

          In allele model, we observed that rs4803420 G and rs1038376 A were related to COPD risk. And rs4803420 G/T and G/T-T/T were related to a decreased COPD risk compared to GG genotype in the co-dominant and dominant models, respectively. When comparing with the AA genotype, rs1038376 A/T and A/T-T/T were associated with an increased COPD risk in the co-dominant and dominant models, respectively. Further gender stratification co-dominant and dominant models analysis showed that genotype G/T and G/T-T/T of rs4803420, and genotype A/T and A/T-T/T of rs1038376 were significantly associated with COPD risk compared to the wide type in males and females, while allele C of rs12979270 was only associated with COPD risk in females. Smoking status stratification analysis showed that rs12979270 C was significantly associated with an increased COPD risk under the allele model compared with allele A in the smoking subgroup. Haplotype analysis showed that haplotype GTA and TAA were related to COPD risk.

          Conclusion

          Our data is the first to demonstrate that CYP2B6 polymorphisms may exert effects on COPD susceptibility in the Chinese Han population.

          Most cited references22

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          Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary.

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            Basic statistical analysis in genetic case-control studies.

            This protocol describes how to perform basic statistical analysis in a population-based genetic association case-control study. The steps described involve the (i) appropriate selection of measures of association and relevance of disease models; (ii) appropriate selection of tests of association; (iii) visualization and interpretation of results; (iv) consideration of appropriate methods to control for multiple testing; and (v) replication strategies. Assuming no previous experience with software such as PLINK, R or Haploview, we describe how to use these popular tools for handling single-nucleotide polymorphism data in order to carry out tests of association and visualize and interpret results. This protocol assumes that data quality assessment and control has been performed, as described in a previous protocol, so that samples and markers deemed to have the potential to introduce bias to the study have been identified and removed. Study design, marker selection and quality control of case-control studies have also been discussed in earlier protocols. The protocol should take ~1 h to complete.
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              Coordinated changes in AHRR methylation in lymphoblasts and pulmonary macrophages from smokers.

              Smoking is associated with a wide variety of adverse health outcomes including cancer, chronic obstructive pulmonary disease, diabetes, depression, and heart disease. Unfortunately, the molecular mechanisms through which these effects are conveyed are not clearly understood. To examine the potential role of epigenetic factors in these processes, we examined the relationship of smoking to genome wide methylation and gene expression using biomaterial from two independent samples, lymphoblast DNA and RNA (n = 119) and lung alveolar macrophage DNA (n = 19). We found that in both samples current smoking status was associated with significant changes in DNA methylation, in particular at the aryl hydrocarbon receptor repressor (AHRR), a known tumor suppressor. Both baseline DNA methylation and smoker associated DNA methylation signatures at AHRR were highly correlated (r = 0.94 and 0.45, respectively). DNA methylation at the most differentially methylated AHRR CpG residue in both samples, cg0557592, was significantly associated with AHRR gene expression. Pathway analysis of lymphoblast data (genes with most significant methylation changes) demonstrated enrichment in protein kinase C pathways and in TGF beta signaling pathways. For alveolar macrophages, pathway analysis demonstrated alterations in inflammation-related processes. We conclude that smoking is associated with functionally significant genome wide changes in DNA methylation in both lymphoblasts and pulmonary macrophages and that further integrated investigations of these epigenetic effects of smoking on carcinogenesis and other related co-morbidities are indicated. Copyright © 2012 Wiley Periodicals, Inc.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                COPD
                copd
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove
                1176-9106
                1178-2005
                05 September 2019
                2019
                : 14
                : 2103-2115
                Affiliations
                [1 ]Department of General Practice, Hainan General Hospital , Haikou, Hainan 570311, People’s Republic of China
                [2 ]Hainan General Hospital, University of South China , Haikou, Hainan 570311, People’s Republic of China
                [3 ]Department of Respiratory Intensive Care Unit (RICU), The First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan 45000, People’s Republic of China
                Author notes
                Correspondence: Yipeng DingDepartment of General Practice, Hainan General Hospital , #19 Xiuhua Road, Haikou, Hainan570311, People’s Republic of ChinaTel/Fax +86 08 986 622 2502Email DingYP66@163.com
                Lihua XingDepartment of Respiratory Intensive Care Unit (RICU), The First Affiliated Hospital of Zhengzhou University , #1 Jianshe East Road, Zhengzhou, Henan45000, People’s Republic of ChinaTel/Fax +86 3 716 696 4992Email xinglihua95088@163.com
                [*]

                These authors contributed equally to this work

                Article
                214961
                10.2147/COPD.S214961
                6733340
                31564857
                ad1f29ab-f34b-4e62-903f-887620374de2
                © 2019 Ding et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 08 May 2019
                : 23 July 2019
                Page count
                Figures: 3, Tables: 7, References: 31, Pages: 13
                Categories
                Original Research

                Respiratory medicine
                cyp2b6,chronic obstructive pulmonary disease,copd,gene polymorphisms,case–control study

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