Cytochrome P450 ( CYP2D6 ) Genotype is Associated with Elevated Systolic Blood Pressure in Preterm Infants after Discharge from the Neonatal Intensive Care Unit
Objective To determine genetic and clinical risk factors associated with elevated systolic blood pressure (ESBP) in preterm infants after discharge from the neonatal intensive care unit (NICU). Study design A convenience cohort of infants born at 90th percentile for term infants). Genetic testing id...
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| Veröffentlicht in: | The Journal of pediatrics 2011-07, Vol.159 (1), p.104-109 |
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| creator | Dagle, John M., MD, PhD Fisher, Tyler J., BA Haynes, Susan E., MD Berends, Susan K., ARNP Brophy, Patrick D., MD Morriss, Frank H., MD, MPH Murray, Jeffrey C., MD |
| description | Objective To determine genetic and clinical risk factors associated with elevated systolic blood pressure (ESBP) in preterm infants after discharge from the neonatal intensive care unit (NICU). Study design A convenience cohort of infants born at 90th percentile for term infants). Genetic testing identified alleles associated with ESBP. Multivariate logistic regression analysis was performed for the outcome ESBP, with clinical characteristics and genotype as independent variables. Results Predictors of ESBP were cytochrome P450, family 2, subfamily D, polypeptide 6 ( CYP2D6 ) (rs28360521) CC genotype (OR, 2.92; 95% CI, 1.48-5.79), adjusted for outpatient oxygen therapy (OR, 4.53; 95% CI, 2.23-8.81) and history of urinary tract infection (OR, 4.68; 95% CI, 1.47-14.86). Maximum SBP was modeled by multivariate linear regression analysis: maximum SBP = 84.8 mm Hg + 6.8 mm Hg if cytochrome P450, family 2, subfamily D, polypeptide 6 ( CYP2D6) CC genotype + 6.8 mm Hg if discharged on supplemental oxygen + 4.4 mm Hg if received inpatient glucocorticoids ( P = .0002). Conclusions ESBP is common in preterm infants with residual lung disease after discharge from the NICU. This study defines clinical factors associated with ESBP, identifies a candidate gene for further testing, and supports the recommendation to monitor blood pressure before age 3 years, as is suggested for term infants. |
| doi_str_mv | 10.1016/j.jpeds.2011.01.002 |
| format | Article |
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Study design A convenience cohort of infants born at <32 weeks gestational age was followed after NICU discharge. We retrospectively identified a subgroup of subjects with ESBP (systolic blood pressure [SBP] >90th percentile for term infants). Genetic testing identified alleles associated with ESBP. Multivariate logistic regression analysis was performed for the outcome ESBP, with clinical characteristics and genotype as independent variables. Results Predictors of ESBP were cytochrome P450, family 2, subfamily D, polypeptide 6 ( CYP2D6 ) (rs28360521) CC genotype (OR, 2.92; 95% CI, 1.48-5.79), adjusted for outpatient oxygen therapy (OR, 4.53; 95% CI, 2.23-8.81) and history of urinary tract infection (OR, 4.68; 95% CI, 1.47-14.86). Maximum SBP was modeled by multivariate linear regression analysis: maximum SBP = 84.8 mm Hg + 6.8 mm Hg if cytochrome P450, family 2, subfamily D, polypeptide 6 ( CYP2D6) CC genotype + 6.8 mm Hg if discharged on supplemental oxygen + 4.4 mm Hg if received inpatient glucocorticoids ( P = .0002). Conclusions ESBP is common in preterm infants with residual lung disease after discharge from the NICU. This study defines clinical factors associated with ESBP, identifies a candidate gene for further testing, and supports the recommendation to monitor blood pressure before age 3 years, as is suggested for term infants.</description><identifier>ISSN: 0022-3476</identifier><identifier>EISSN: 1097-6833</identifier><identifier>DOI: 10.1016/j.jpeds.2011.01.002</identifier><identifier>PMID: 21353244</identifier><identifier>CODEN: JOPDAB</identifier><language>eng</language><publisher>Maryland Heights, MO: Elsevier Inc</publisher><subject>alleles ; Arterial hypertension. Arterial hypotension ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cohort Studies ; cytochrome P-450 ; Cytochrome P-450 CYP2D6 - genetics ; Female ; Gene Frequency ; General aspects ; Genotype ; gestational age ; glucocorticoids ; Glucocorticoids - therapeutic use ; Humans ; Hypertension - epidemiology ; Hypertension - genetics ; Infant, Newborn ; Infant, Premature ; infants ; Intensive Care Units, Neonatal ; linear models ; Male ; Medical sciences ; Multivariate Analysis ; oxygen ; Oxygen Inhalation Therapy ; Patient Discharge ; Pediatrics ; Polymorphism, Single Nucleotide ; polypeptides ; regression analysis ; Retrospective Studies ; risk factors ; Systole ; systolic blood pressure ; therapeutics ; urinary tract diseases ; Urinary Tract Infections - epidemiology</subject><ispartof>The Journal of pediatrics, 2011-07, Vol.159 (1), p.104-109</ispartof><rights>Mosby, Inc.</rights><rights>2011 Mosby, Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Mosby, Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c512t-93ad1708d4515c59a3bfa41748c674291f2a4aa5a2262ace207f5e34ebdebd503</citedby><cites>FETCH-LOGICAL-c512t-93ad1708d4515c59a3bfa41748c674291f2a4aa5a2262ace207f5e34ebdebd503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jpeds.2011.01.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3541,27915,27916,45986</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24289299$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21353244$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dagle, John M., MD, PhD</creatorcontrib><creatorcontrib>Fisher, Tyler J., BA</creatorcontrib><creatorcontrib>Haynes, Susan E., MD</creatorcontrib><creatorcontrib>Berends, Susan K., ARNP</creatorcontrib><creatorcontrib>Brophy, Patrick D., MD</creatorcontrib><creatorcontrib>Morriss, Frank H., MD, MPH</creatorcontrib><creatorcontrib>Murray, Jeffrey C., MD</creatorcontrib><title>Cytochrome P450 ( CYP2D6 ) Genotype is Associated with Elevated Systolic Blood Pressure in Preterm Infants after Discharge from the Neonatal Intensive Care Unit</title><title>The Journal of pediatrics</title><addtitle>J Pediatr</addtitle><description>Objective To determine genetic and clinical risk factors associated with elevated systolic blood pressure (ESBP) in preterm infants after discharge from the neonatal intensive care unit (NICU). Study design A convenience cohort of infants born at <32 weeks gestational age was followed after NICU discharge. We retrospectively identified a subgroup of subjects with ESBP (systolic blood pressure [SBP] >90th percentile for term infants). Genetic testing identified alleles associated with ESBP. Multivariate logistic regression analysis was performed for the outcome ESBP, with clinical characteristics and genotype as independent variables. Results Predictors of ESBP were cytochrome P450, family 2, subfamily D, polypeptide 6 ( CYP2D6 ) (rs28360521) CC genotype (OR, 2.92; 95% CI, 1.48-5.79), adjusted for outpatient oxygen therapy (OR, 4.53; 95% CI, 2.23-8.81) and history of urinary tract infection (OR, 4.68; 95% CI, 1.47-14.86). Maximum SBP was modeled by multivariate linear regression analysis: maximum SBP = 84.8 mm Hg + 6.8 mm Hg if cytochrome P450, family 2, subfamily D, polypeptide 6 ( CYP2D6) CC genotype + 6.8 mm Hg if discharged on supplemental oxygen + 4.4 mm Hg if received inpatient glucocorticoids ( P = .0002). Conclusions ESBP is common in preterm infants with residual lung disease after discharge from the NICU. This study defines clinical factors associated with ESBP, identifies a candidate gene for further testing, and supports the recommendation to monitor blood pressure before age 3 years, as is suggested for term infants.</description><subject>alleles</subject><subject>Arterial hypertension. Arterial hypotension</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cohort Studies</subject><subject>cytochrome P-450</subject><subject>Cytochrome P-450 CYP2D6 - genetics</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>General aspects</subject><subject>Genotype</subject><subject>gestational age</subject><subject>glucocorticoids</subject><subject>Glucocorticoids - therapeutic use</subject><subject>Humans</subject><subject>Hypertension - epidemiology</subject><subject>Hypertension - genetics</subject><subject>Infant, Newborn</subject><subject>Infant, Premature</subject><subject>infants</subject><subject>Intensive Care Units, Neonatal</subject><subject>linear models</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Multivariate Analysis</subject><subject>oxygen</subject><subject>Oxygen Inhalation Therapy</subject><subject>Patient Discharge</subject><subject>Pediatrics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>polypeptides</subject><subject>regression analysis</subject><subject>Retrospective Studies</subject><subject>risk factors</subject><subject>Systole</subject><subject>systolic blood pressure</subject><subject>therapeutics</subject><subject>urinary tract diseases</subject><subject>Urinary Tract Infections - epidemiology</subject><issn>0022-3476</issn><issn>1097-6833</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkstuUzEQho8QiJbCEyCBNwhYJPh2bguQSlpKpQoihS5YWVOfOY3DiR1sJyhvw6MyaQJIbJBGssf6ZuaX_ymKp4KPBRfVm8V4scIujSUXYswpuLxXHAve1qOqUep-cUwvcqR0XR0Vj1JacM5bzfnD4kgKVSqp9XHxc7LNwc5jWCKb6pKzV2zydSrPKvaaXaAPebtC5hI7TSlYBxk79sPlOTsfcHOXzbYph8FZ9n4IoWPTiCmtI9X43T1jXLJL34PPiUFPKTtzyc4h3iLraSrLc2SfMHjIMBCZ0Se3QTYB6nHtXX5cPOhhSPjkcJ4U1x_Ov0w-jq4-X1xOTq9GthQyj1oFnah50-lSlLZsQd30oEWtG1vVWrail6ABSpCykmBR8rovUWm86ShKrk6Kl_u-qxi-rzFlsyShOAzgMayTaWrRVk3TCCLVnrQxpBSxN6volhC3RnCzc8YszJ0zZueM4RRcUtWzQ__1zRK7PzW_rSDgxQGAZGHoI3jr0l9Oy6aVbUvc8z3XQzBwG4m5ntGkkuxtaqkrIt7uCaT_2jiMJlmH3mLnItpsuuD-I_XdP_V2cN6RqG-4xbQI6-jJCiNMkoab2W7NdlsmBEkQqlG_ANaeyv0</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>Dagle, John M., MD, PhD</creator><creator>Fisher, Tyler J., BA</creator><creator>Haynes, Susan E., MD</creator><creator>Berends, Susan K., ARNP</creator><creator>Brophy, Patrick D., MD</creator><creator>Morriss, Frank H., MD, MPH</creator><creator>Murray, Jeffrey C., MD</creator><general>Elsevier Inc</general><general>Mosby, Inc</general><general>Elsevier</general><scope>FBQ</scope><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20110701</creationdate><title>Cytochrome P450 ( CYP2D6 ) Genotype is Associated with Elevated Systolic Blood Pressure in Preterm Infants after Discharge from the Neonatal Intensive Care Unit</title><author>Dagle, John M., MD, PhD ; Fisher, Tyler J., BA ; Haynes, Susan E., MD ; Berends, Susan K., ARNP ; Brophy, Patrick D., MD ; Morriss, Frank H., MD, MPH ; Murray, Jeffrey C., MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c512t-93ad1708d4515c59a3bfa41748c674291f2a4aa5a2262ace207f5e34ebdebd503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>alleles</topic><topic>Arterial hypertension. Arterial hypotension</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cohort Studies</topic><topic>cytochrome P-450</topic><topic>Cytochrome P-450 CYP2D6 - genetics</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>General aspects</topic><topic>Genotype</topic><topic>gestational age</topic><topic>glucocorticoids</topic><topic>Glucocorticoids - therapeutic use</topic><topic>Humans</topic><topic>Hypertension - epidemiology</topic><topic>Hypertension - genetics</topic><topic>Infant, Newborn</topic><topic>Infant, Premature</topic><topic>infants</topic><topic>Intensive Care Units, Neonatal</topic><topic>linear models</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Multivariate Analysis</topic><topic>oxygen</topic><topic>Oxygen Inhalation Therapy</topic><topic>Patient Discharge</topic><topic>Pediatrics</topic><topic>Polymorphism, Single Nucleotide</topic><topic>polypeptides</topic><topic>regression analysis</topic><topic>Retrospective Studies</topic><topic>risk factors</topic><topic>Systole</topic><topic>systolic blood pressure</topic><topic>therapeutics</topic><topic>urinary tract diseases</topic><topic>Urinary Tract Infections - epidemiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dagle, John M., MD, PhD</creatorcontrib><creatorcontrib>Fisher, Tyler J., BA</creatorcontrib><creatorcontrib>Haynes, Susan E., MD</creatorcontrib><creatorcontrib>Berends, Susan K., ARNP</creatorcontrib><creatorcontrib>Brophy, Patrick D., MD</creatorcontrib><creatorcontrib>Morriss, Frank H., MD, MPH</creatorcontrib><creatorcontrib>Murray, Jeffrey C., MD</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of pediatrics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dagle, John M., MD, PhD</au><au>Fisher, Tyler J., BA</au><au>Haynes, Susan E., MD</au><au>Berends, Susan K., ARNP</au><au>Brophy, Patrick D., MD</au><au>Morriss, Frank H., MD, MPH</au><au>Murray, Jeffrey C., MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytochrome P450 ( CYP2D6 ) Genotype is Associated with Elevated Systolic Blood Pressure in Preterm Infants after Discharge from the Neonatal Intensive Care Unit</atitle><jtitle>The Journal of pediatrics</jtitle><addtitle>J Pediatr</addtitle><date>2011-07-01</date><risdate>2011</risdate><volume>159</volume><issue>1</issue><spage>104</spage><epage>109</epage><pages>104-109</pages><issn>0022-3476</issn><eissn>1097-6833</eissn><coden>JOPDAB</coden><abstract>Objective To determine genetic and clinical risk factors associated with elevated systolic blood pressure (ESBP) in preterm infants after discharge from the neonatal intensive care unit (NICU). Study design A convenience cohort of infants born at <32 weeks gestational age was followed after NICU discharge. We retrospectively identified a subgroup of subjects with ESBP (systolic blood pressure [SBP] >90th percentile for term infants). Genetic testing identified alleles associated with ESBP. Multivariate logistic regression analysis was performed for the outcome ESBP, with clinical characteristics and genotype as independent variables. Results Predictors of ESBP were cytochrome P450, family 2, subfamily D, polypeptide 6 ( CYP2D6 ) (rs28360521) CC genotype (OR, 2.92; 95% CI, 1.48-5.79), adjusted for outpatient oxygen therapy (OR, 4.53; 95% CI, 2.23-8.81) and history of urinary tract infection (OR, 4.68; 95% CI, 1.47-14.86). Maximum SBP was modeled by multivariate linear regression analysis: maximum SBP = 84.8 mm Hg + 6.8 mm Hg if cytochrome P450, family 2, subfamily D, polypeptide 6 ( CYP2D6) CC genotype + 6.8 mm Hg if discharged on supplemental oxygen + 4.4 mm Hg if received inpatient glucocorticoids ( P = .0002). Conclusions ESBP is common in preterm infants with residual lung disease after discharge from the NICU. This study defines clinical factors associated with ESBP, identifies a candidate gene for further testing, and supports the recommendation to monitor blood pressure before age 3 years, as is suggested for term infants.</abstract><cop>Maryland Heights, MO</cop><pub>Elsevier Inc</pub><pmid>21353244</pmid><doi>10.1016/j.jpeds.2011.01.002</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | alleles Arterial hypertension. Arterial hypotension Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cohort Studies cytochrome P-450 Cytochrome P-450 CYP2D6 - genetics Female Gene Frequency General aspects Genotype gestational age glucocorticoids Glucocorticoids - therapeutic use Humans Hypertension - epidemiology Hypertension - genetics Infant, Newborn Infant, Premature infants Intensive Care Units, Neonatal linear models Male Medical sciences Multivariate Analysis oxygen Oxygen Inhalation Therapy Patient Discharge Pediatrics Polymorphism, Single Nucleotide polypeptides regression analysis Retrospective Studies risk factors Systole systolic blood pressure therapeutics urinary tract diseases Urinary Tract Infections - epidemiology |
| title | Cytochrome P450 ( CYP2D6 ) Genotype is Associated with Elevated Systolic Blood Pressure in Preterm Infants after Discharge from the Neonatal Intensive Care Unit |
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