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A functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity
Cigarette smoke exposure is the leading modifiable risk factor for chronic obstructive pulmonary disease (COPD); however, the clinical and pathologic consequences of chronic cigarette smoke exposure are variable among smokers. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine im...
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| Published in: | American journal of physiology. Lung cellular and molecular physiology 2019-02, Vol.316 (2), p.L400-L405 |
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| container_title | American journal of physiology. Lung cellular and molecular physiology |
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| creator | Zhang, C Ramsey, C Berical, A Yu, L Leng, L McGinnis, K A Song, Y Michael, H McCormack, M C Allore, H Morris, A Crothers, K Bucala, R Lee, P J Sauler, M |
| description | Cigarette smoke exposure is the leading modifiable risk factor for chronic obstructive pulmonary disease (COPD); however, the clinical and pathologic consequences of chronic cigarette smoke exposure are variable among smokers. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in the pathogenesis of COPD. Within the promoter of the MIF gene is a functional polymorphism that regulates MIF expression (-794 CATT
microsatellite repeat) ( rs5844572 ). The role of this polymorphim in mediating disease susceptibility to COPD-related traits remains unknown. We performed a cross-sectional analysis of DNA samples from 641 subjects to analyze MIF-794 CATT
( rs5844572 ) polymorphism by standard methods. We generated multivariable logistic regression models to determine the risk of low expressing MIF alleles for airflow obstruction [defined by forced expiratory volume in 1 s (FEV
)/forced vital capacity ratio |
| doi_str_mv | 10.1152/ajplung.00439.2018 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6397351</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2185041522</sourcerecordid><originalsourceid>FETCH-LOGICAL-c430t-1882ddbd744565caae2f2cebd981d8293730d6c56e6f8a18a49c28d85f208bfd3</originalsourceid><addsrcrecordid>eNpdkU1v1DAQhiNERUvLH-CALHHhku3YjrPOBamqyodUiQs9WxN_JF4lcbATqv33OHSpgNPMeN555ZmnKN5S2FEq2DUe5mGduh1AxZsdAypfFBe5wUoqoHqZc6ighBrEefE6pQMACID6VXHOQTCoZXNRPN4Qt0568WHCgYyoY5h77CwZfRdxeyZ-6n3rlxCPxKHOkcwxjGGxOQnDcQxx7n0aiU8EUwra42INefRLT6I1q86F8c6tyU8d0Tij9svxqjhzOCT75hQvi4dPd99vv5T33z5_vb25L3XFYSmplMyY1uyrStRCI1rmmLataSQ1kjV8z8HUWtS2dhKpxKrRTBopHAPZOsMvi49PvvPajtZoOy0RBzVHP2I8qoBe_duZfK-68FPVvNlzQbPBh5NBDD9WmxY1-qTtMOBkw5oUo_uG8YrKKkvf_yc9hDXmu24qmZFsbLKKPanyqVOK1j1_hoLauKoTV_Wbq9q45qF3f6_xPPIHJP8FTbWkdw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2185041522</pqid></control><display><type>article</type><title>A functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity</title><source>American Physiological Society Free</source><creator>Zhang, C ; Ramsey, C ; Berical, A ; Yu, L ; Leng, L ; McGinnis, K A ; Song, Y ; Michael, H ; McCormack, M C ; Allore, H ; Morris, A ; Crothers, K ; Bucala, R ; Lee, P J ; Sauler, M</creator><creatorcontrib>Zhang, C ; Ramsey, C ; Berical, A ; Yu, L ; Leng, L ; McGinnis, K A ; Song, Y ; Michael, H ; McCormack, M C ; Allore, H ; Morris, A ; Crothers, K ; Bucala, R ; Lee, P J ; Sauler, M</creatorcontrib><description>Cigarette smoke exposure is the leading modifiable risk factor for chronic obstructive pulmonary disease (COPD); however, the clinical and pathologic consequences of chronic cigarette smoke exposure are variable among smokers. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in the pathogenesis of COPD. Within the promoter of the MIF gene is a functional polymorphism that regulates MIF expression (-794 CATT
microsatellite repeat) ( rs5844572 ). The role of this polymorphim in mediating disease susceptibility to COPD-related traits remains unknown. We performed a cross-sectional analysis of DNA samples from 641 subjects to analyze MIF-794 CATT
( rs5844572 ) polymorphism by standard methods. We generated multivariable logistic regression models to determine the risk of low expressing MIF alleles for airflow obstruction [defined by forced expiratory volume in 1 s (FEV
)/forced vital capacity ratio <0.70] and an abnormal diffusion capacity [defined by a diffusion capacity for carbon monoxide (DL
) percent predicted <80%]. We then used generalized linear models to determine the association of MIF genotypes with FEV
percent predicted and DL
percent predicted. The MIF-794 CATT
allele was associated with an abnormal diffusion capacity in two cohorts [odds ratio (OR): 9.31, 95% confidence interval (CI): 1.97-4.06; and OR: 2.21, 95% CI: 1.03-4.75]. Similarly, the MIF-794 CATT
allele was associated with a reduced DL
percentage predicted in these two cohorts: 63.5 vs. 70.0 ( P = 0.0023) and 60.1 vs. 65.4 ( P = 0.059). This study suggests an association between a common genetic polymorphism of an endogenous innate immune gene, MIF, with reduced DL
, an important measurement of COPD severity.</description><identifier>ISSN: 1040-0605</identifier><identifier>EISSN: 1522-1504</identifier><identifier>DOI: 10.1152/ajplung.00439.2018</identifier><identifier>PMID: 30520689</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Air flow ; Alleles ; Carbon monoxide ; Chronic obstructive pulmonary disease ; Cigarette smoke ; Confidence intervals ; Deoxyribonucleic acid ; Diffusion ; DNA ; Exposure ; Forced Expiratory Volume - genetics ; Gene expression ; Gene polymorphism ; Generalized linear models ; Genetic Predisposition to Disease - genetics ; Genotypes ; Health risk assessment ; Health risks ; Leukocyte migration ; Lung - metabolism ; Lung diseases ; Macrophage migration inhibitory factor ; Macrophage Migration-Inhibitory Factors - genetics ; Macrophage Migration-Inhibitory Factors - metabolism ; Obstructive lung disease ; Pathogenesis ; Polymorphism ; Polymorphism, Single Nucleotide - genetics ; Promoter Regions, Genetic - genetics ; Pulmonary Disease, Chronic Obstructive - genetics ; Pulmonary Disease, Chronic Obstructive - metabolism ; Rapid Report ; Regression analysis ; Regression models ; Respiratory Function Tests ; Risk analysis ; Risk factors ; Smoke ; Smoke - adverse effects ; Statistical analysis ; Statistical models ; Tobacco smoke ; Vital Capacity - genetics ; Vital Capacity - physiology</subject><ispartof>American journal of physiology. Lung cellular and molecular physiology, 2019-02, Vol.316 (2), p.L400-L405</ispartof><rights>Copyright American Physiological Society Feb 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-1882ddbd744565caae2f2cebd981d8293730d6c56e6f8a18a49c28d85f208bfd3</citedby><cites>FETCH-LOGICAL-c430t-1882ddbd744565caae2f2cebd981d8293730d6c56e6f8a18a49c28d85f208bfd3</cites><orcidid>0000-0001-5240-7978</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30520689$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, C</creatorcontrib><creatorcontrib>Ramsey, C</creatorcontrib><creatorcontrib>Berical, A</creatorcontrib><creatorcontrib>Yu, L</creatorcontrib><creatorcontrib>Leng, L</creatorcontrib><creatorcontrib>McGinnis, K A</creatorcontrib><creatorcontrib>Song, Y</creatorcontrib><creatorcontrib>Michael, H</creatorcontrib><creatorcontrib>McCormack, M C</creatorcontrib><creatorcontrib>Allore, H</creatorcontrib><creatorcontrib>Morris, A</creatorcontrib><creatorcontrib>Crothers, K</creatorcontrib><creatorcontrib>Bucala, R</creatorcontrib><creatorcontrib>Lee, P J</creatorcontrib><creatorcontrib>Sauler, M</creatorcontrib><title>A functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity</title><title>American journal of physiology. Lung cellular and molecular physiology</title><addtitle>Am J Physiol Lung Cell Mol Physiol</addtitle><description>Cigarette smoke exposure is the leading modifiable risk factor for chronic obstructive pulmonary disease (COPD); however, the clinical and pathologic consequences of chronic cigarette smoke exposure are variable among smokers. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in the pathogenesis of COPD. Within the promoter of the MIF gene is a functional polymorphism that regulates MIF expression (-794 CATT
microsatellite repeat) ( rs5844572 ). The role of this polymorphim in mediating disease susceptibility to COPD-related traits remains unknown. We performed a cross-sectional analysis of DNA samples from 641 subjects to analyze MIF-794 CATT
( rs5844572 ) polymorphism by standard methods. We generated multivariable logistic regression models to determine the risk of low expressing MIF alleles for airflow obstruction [defined by forced expiratory volume in 1 s (FEV
)/forced vital capacity ratio <0.70] and an abnormal diffusion capacity [defined by a diffusion capacity for carbon monoxide (DL
) percent predicted <80%]. We then used generalized linear models to determine the association of MIF genotypes with FEV
percent predicted and DL
percent predicted. The MIF-794 CATT
allele was associated with an abnormal diffusion capacity in two cohorts [odds ratio (OR): 9.31, 95% confidence interval (CI): 1.97-4.06; and OR: 2.21, 95% CI: 1.03-4.75]. Similarly, the MIF-794 CATT
allele was associated with a reduced DL
percentage predicted in these two cohorts: 63.5 vs. 70.0 ( P = 0.0023) and 60.1 vs. 65.4 ( P = 0.059). This study suggests an association between a common genetic polymorphism of an endogenous innate immune gene, MIF, with reduced DL
, an important measurement of COPD severity.</description><subject>Air flow</subject><subject>Alleles</subject><subject>Carbon monoxide</subject><subject>Chronic obstructive pulmonary disease</subject><subject>Cigarette smoke</subject><subject>Confidence intervals</subject><subject>Deoxyribonucleic acid</subject><subject>Diffusion</subject><subject>DNA</subject><subject>Exposure</subject><subject>Forced Expiratory Volume - genetics</subject><subject>Gene expression</subject><subject>Gene polymorphism</subject><subject>Generalized linear models</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genotypes</subject><subject>Health risk assessment</subject><subject>Health risks</subject><subject>Leukocyte migration</subject><subject>Lung - metabolism</subject><subject>Lung diseases</subject><subject>Macrophage migration inhibitory factor</subject><subject>Macrophage Migration-Inhibitory Factors - genetics</subject><subject>Macrophage Migration-Inhibitory Factors - metabolism</subject><subject>Obstructive lung disease</subject><subject>Pathogenesis</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Pulmonary Disease, Chronic Obstructive - genetics</subject><subject>Pulmonary Disease, Chronic Obstructive - metabolism</subject><subject>Rapid Report</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Respiratory Function Tests</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Smoke</subject><subject>Smoke - adverse effects</subject><subject>Statistical analysis</subject><subject>Statistical models</subject><subject>Tobacco smoke</subject><subject>Vital Capacity - genetics</subject><subject>Vital Capacity - physiology</subject><issn>1040-0605</issn><issn>1522-1504</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpdkU1v1DAQhiNERUvLH-CALHHhku3YjrPOBamqyodUiQs9WxN_JF4lcbATqv33OHSpgNPMeN555ZmnKN5S2FEq2DUe5mGduh1AxZsdAypfFBe5wUoqoHqZc6ighBrEefE6pQMACID6VXHOQTCoZXNRPN4Qt0568WHCgYyoY5h77CwZfRdxeyZ-6n3rlxCPxKHOkcwxjGGxOQnDcQxx7n0aiU8EUwra42INefRLT6I1q86F8c6tyU8d0Tij9svxqjhzOCT75hQvi4dPd99vv5T33z5_vb25L3XFYSmplMyY1uyrStRCI1rmmLataSQ1kjV8z8HUWtS2dhKpxKrRTBopHAPZOsMvi49PvvPajtZoOy0RBzVHP2I8qoBe_duZfK-68FPVvNlzQbPBh5NBDD9WmxY1-qTtMOBkw5oUo_uG8YrKKkvf_yc9hDXmu24qmZFsbLKKPanyqVOK1j1_hoLauKoTV_Wbq9q45qF3f6_xPPIHJP8FTbWkdw</recordid><startdate>20190201</startdate><enddate>20190201</enddate><creator>Zhang, C</creator><creator>Ramsey, C</creator><creator>Berical, A</creator><creator>Yu, L</creator><creator>Leng, L</creator><creator>McGinnis, K A</creator><creator>Song, Y</creator><creator>Michael, H</creator><creator>McCormack, M C</creator><creator>Allore, H</creator><creator>Morris, A</creator><creator>Crothers, K</creator><creator>Bucala, R</creator><creator>Lee, P J</creator><creator>Sauler, M</creator><general>American Physiological Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TS</scope><scope>7U7</scope><scope>C1K</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5240-7978</orcidid></search><sort><creationdate>20190201</creationdate><title>A functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity</title><author>Zhang, C ; Ramsey, C ; Berical, A ; Yu, L ; Leng, L ; McGinnis, K A ; Song, Y ; Michael, H ; McCormack, M C ; Allore, H ; Morris, A ; Crothers, K ; Bucala, R ; Lee, P J ; Sauler, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-1882ddbd744565caae2f2cebd981d8293730d6c56e6f8a18a49c28d85f208bfd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Air flow</topic><topic>Alleles</topic><topic>Carbon monoxide</topic><topic>Chronic obstructive pulmonary disease</topic><topic>Cigarette smoke</topic><topic>Confidence intervals</topic><topic>Deoxyribonucleic acid</topic><topic>Diffusion</topic><topic>DNA</topic><topic>Exposure</topic><topic>Forced Expiratory Volume - genetics</topic><topic>Gene expression</topic><topic>Gene polymorphism</topic><topic>Generalized linear models</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genotypes</topic><topic>Health risk assessment</topic><topic>Health risks</topic><topic>Leukocyte migration</topic><topic>Lung - metabolism</topic><topic>Lung diseases</topic><topic>Macrophage migration inhibitory factor</topic><topic>Macrophage Migration-Inhibitory Factors - genetics</topic><topic>Macrophage Migration-Inhibitory Factors - metabolism</topic><topic>Obstructive lung disease</topic><topic>Pathogenesis</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Pulmonary Disease, Chronic Obstructive - genetics</topic><topic>Pulmonary Disease, Chronic Obstructive - metabolism</topic><topic>Rapid Report</topic><topic>Regression analysis</topic><topic>Regression models</topic><topic>Respiratory Function Tests</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Smoke</topic><topic>Smoke - adverse effects</topic><topic>Statistical analysis</topic><topic>Statistical models</topic><topic>Tobacco smoke</topic><topic>Vital Capacity - genetics</topic><topic>Vital Capacity - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, C</creatorcontrib><creatorcontrib>Ramsey, C</creatorcontrib><creatorcontrib>Berical, A</creatorcontrib><creatorcontrib>Yu, L</creatorcontrib><creatorcontrib>Leng, L</creatorcontrib><creatorcontrib>McGinnis, K A</creatorcontrib><creatorcontrib>Song, Y</creatorcontrib><creatorcontrib>Michael, H</creatorcontrib><creatorcontrib>McCormack, M C</creatorcontrib><creatorcontrib>Allore, H</creatorcontrib><creatorcontrib>Morris, A</creatorcontrib><creatorcontrib>Crothers, K</creatorcontrib><creatorcontrib>Bucala, R</creatorcontrib><creatorcontrib>Lee, P J</creatorcontrib><creatorcontrib>Sauler, M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of physiology. Lung cellular and molecular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, C</au><au>Ramsey, C</au><au>Berical, A</au><au>Yu, L</au><au>Leng, L</au><au>McGinnis, K A</au><au>Song, Y</au><au>Michael, H</au><au>McCormack, M C</au><au>Allore, H</au><au>Morris, A</au><au>Crothers, K</au><au>Bucala, R</au><au>Lee, P J</au><au>Sauler, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity</atitle><jtitle>American journal of physiology. Lung cellular and molecular physiology</jtitle><addtitle>Am J Physiol Lung Cell Mol Physiol</addtitle><date>2019-02-01</date><risdate>2019</risdate><volume>316</volume><issue>2</issue><spage>L400</spage><epage>L405</epage><pages>L400-L405</pages><issn>1040-0605</issn><eissn>1522-1504</eissn><abstract>Cigarette smoke exposure is the leading modifiable risk factor for chronic obstructive pulmonary disease (COPD); however, the clinical and pathologic consequences of chronic cigarette smoke exposure are variable among smokers. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in the pathogenesis of COPD. Within the promoter of the MIF gene is a functional polymorphism that regulates MIF expression (-794 CATT
microsatellite repeat) ( rs5844572 ). The role of this polymorphim in mediating disease susceptibility to COPD-related traits remains unknown. We performed a cross-sectional analysis of DNA samples from 641 subjects to analyze MIF-794 CATT
( rs5844572 ) polymorphism by standard methods. We generated multivariable logistic regression models to determine the risk of low expressing MIF alleles for airflow obstruction [defined by forced expiratory volume in 1 s (FEV
)/forced vital capacity ratio <0.70] and an abnormal diffusion capacity [defined by a diffusion capacity for carbon monoxide (DL
) percent predicted <80%]. We then used generalized linear models to determine the association of MIF genotypes with FEV
percent predicted and DL
percent predicted. The MIF-794 CATT
allele was associated with an abnormal diffusion capacity in two cohorts [odds ratio (OR): 9.31, 95% confidence interval (CI): 1.97-4.06; and OR: 2.21, 95% CI: 1.03-4.75]. Similarly, the MIF-794 CATT
allele was associated with a reduced DL
percentage predicted in these two cohorts: 63.5 vs. 70.0 ( P = 0.0023) and 60.1 vs. 65.4 ( P = 0.059). This study suggests an association between a common genetic polymorphism of an endogenous innate immune gene, MIF, with reduced DL
, an important measurement of COPD severity.</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>30520689</pmid><doi>10.1152/ajplung.00439.2018</doi><orcidid>https://orcid.org/0000-0001-5240-7978</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | American journal of physiology. Lung cellular and molecular physiology, 2019-02, Vol.316 (2), p.L400-L405 |
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| source | American Physiological Society Free |
| subjects | Air flow Alleles Carbon monoxide Chronic obstructive pulmonary disease Cigarette smoke Confidence intervals Deoxyribonucleic acid Diffusion DNA Exposure Forced Expiratory Volume - genetics Gene expression Gene polymorphism Generalized linear models Genetic Predisposition to Disease - genetics Genotypes Health risk assessment Health risks Leukocyte migration Lung - metabolism Lung diseases Macrophage migration inhibitory factor Macrophage Migration-Inhibitory Factors - genetics Macrophage Migration-Inhibitory Factors - metabolism Obstructive lung disease Pathogenesis Polymorphism Polymorphism, Single Nucleotide - genetics Promoter Regions, Genetic - genetics Pulmonary Disease, Chronic Obstructive - genetics Pulmonary Disease, Chronic Obstructive - metabolism Rapid Report Regression analysis Regression models Respiratory Function Tests Risk analysis Risk factors Smoke Smoke - adverse effects Statistical analysis Statistical models Tobacco smoke Vital Capacity - genetics Vital Capacity - physiology |
| title | A functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity |
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