Genetic and metabolic predictors of hepatic fat content in a cohort of Italian children with obesity
Objectives To comprehensively explore metabolic and genetic contributors to liver fat accumulation in overweight/obese children. Methods Two hundred thirty Italian children with obesity were investigated for metabolic parameters and genotyped for PNPLA3 , TM6SF2 , GCKR , and MBOAT7 gene variants. Pe...
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| Veröffentlicht in: | Pediatric research 2019-04, Vol.85 (5), p.671-677 |
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| creator | Di Costanzo, Alessia Pacifico, Lucia Chiesa, Claudio Perla, Francesco Massimo Ceci, Fabrizio Angeloni, Antonio D’Erasmo, Laura Di Martino, Michele Arca, Marcello |
| description | Objectives
To comprehensively explore metabolic and genetic contributors to liver fat accumulation in overweight/obese children.
Methods
Two hundred thirty Italian children with obesity were investigated for metabolic parameters and genotyped for
PNPLA3
,
TM6SF2
,
GCKR
, and
MBOAT7
gene variants. Percentage hepatic fat content (HFF%) was measured by nuclear magnetic resonance.
Results
HFF% was positively related with BMI, HOMA
IR
, metabolic syndrome, ALT, AST, γGT, and albumin. Carriers of [G] allele in
PNPLA3
, [T] allele in
GCKR
and [T] allele in
TM6SF2
genes had significantly higher hepatic fat content than wild-type carriers. HFF% was explained for 8.7% by metabolic and for 16.1% by genetic factors and, a model including age, gender, BMI, HOMA
IR
,
PNPLA3
,
GCKR
, and
TM6SF2
variants was the best predictor of HFF%, explaining 24.8% of its variation (
P
|
| doi_str_mv | 10.1038/s41390-019-0303-1 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6760560</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2179500682</sourcerecordid><originalsourceid>FETCH-LOGICAL-c470t-5aed96a9ec75f48a35da438641a5db9553329f0f013567cbf7682c49f62a28d73</originalsourceid><addsrcrecordid>eNp1kU1vFDEMhiMEotvCD-CCInHhMmBPkklyQUIVtJUqcYFzlMlkOqlmkyXJUvXfk9WW8iFxsmw_fm3rJeQVwjsEpt4XjkxDB6g7YMA6fEI2KFircC6fkg0Aw45prU7IaSm3AMiF4s_JCQOJgCg2ZLrw0dfgqI0T3fpqx7S2bJf9FFxNudA008Xv7IGZbaUuxepjpSFS25Il5XpArqpdg43ULWGdso_0LtSFptGXUO9fkGezXYt_-RDPyLfPn76eX3bXXy6uzj9ed45LqJ2wftKD1d5JMXNlmZgsZ2rgaMU0aiEY6_UMMyATg3TjLAfVO67nobe9miQ7Ix-Ourv9uPWTa3dmu5pdDlub702ywfzdiWExN-mHGeQAYoAm8PZBIKfve1-q2Ybi_Lra6NO-mB6lFgBtbUPf_IPepn2O7b1GacmwV6gahUfK5VRK9vPjMQjm4KE5emiah-bgocE28_rPLx4nfpnWgP4IlNaKNz7_Xv1_1Z-byKeJ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2197312818</pqid></control><display><type>article</type><title>Genetic and metabolic predictors of hepatic fat content in a cohort of Italian children with obesity</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Di Costanzo, Alessia ; Pacifico, Lucia ; Chiesa, Claudio ; Perla, Francesco Massimo ; Ceci, Fabrizio ; Angeloni, Antonio ; D’Erasmo, Laura ; Di Martino, Michele ; Arca, Marcello</creator><creatorcontrib>Di Costanzo, Alessia ; Pacifico, Lucia ; Chiesa, Claudio ; Perla, Francesco Massimo ; Ceci, Fabrizio ; Angeloni, Antonio ; D’Erasmo, Laura ; Di Martino, Michele ; Arca, Marcello</creatorcontrib><description>Objectives
To comprehensively explore metabolic and genetic contributors to liver fat accumulation in overweight/obese children.
Methods
Two hundred thirty Italian children with obesity were investigated for metabolic parameters and genotyped for
PNPLA3
,
TM6SF2
,
GCKR
, and
MBOAT7
gene variants. Percentage hepatic fat content (HFF%) was measured by nuclear magnetic resonance.
Results
HFF% was positively related with BMI, HOMA
IR
, metabolic syndrome, ALT, AST, γGT, and albumin. Carriers of [G] allele in
PNPLA3
, [T] allele in
GCKR
and [T] allele in
TM6SF2
genes had significantly higher hepatic fat content than wild-type carriers. HFF% was explained for 8.7% by metabolic and for 16.1% by genetic factors and, a model including age, gender, BMI, HOMA
IR
,
PNPLA3
,
GCKR
, and
TM6SF2
variants was the best predictor of HFF%, explaining 24.8% of its variation (
P
< 0.001). A weighted-genetic risk score combining
PNPLA3
,
GCKR,
and
TM6SF2
risk alleles was associated with almost eightfold higher risk of NAFLD.
Conclusions
Our data highlighted the predominant role of genetic factors in determining the amount of liver fat content in children with obesity.</description><identifier>ISSN: 0031-3998</identifier><identifier>EISSN: 1530-0447</identifier><identifier>DOI: 10.1038/s41390-019-0303-1</identifier><identifier>PMID: 30710115</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Acyltransferases - genetics ; Adaptor Proteins, Signal Transducing - genetics ; Adipose Tissue - metabolism ; Adolescent ; Alleles ; Body Mass Index ; Child ; Clinical ; Clinical Research Article ; DNA - analysis ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Genotype ; Humans ; Italy - epidemiology ; Lipase - genetics ; Liver - diagnostic imaging ; Liver - pathology ; Magnetic Resonance Spectroscopy ; Male ; Medicine ; Medicine & Public Health ; Membrane Proteins - genetics ; Metabolism ; Non-alcoholic Fatty Liver Disease - diagnostic imaging ; Non-alcoholic Fatty Liver Disease - genetics ; Obesity ; Overweight ; Pediatric Obesity - epidemiology ; Pediatric Obesity - genetics ; Pediatric Surgery ; Pediatrics ; Risk</subject><ispartof>Pediatric research, 2019-04, Vol.85 (5), p.671-677</ispartof><rights>The Author(s) 2019</rights><rights>This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-5aed96a9ec75f48a35da438641a5db9553329f0f013567cbf7682c49f62a28d73</citedby><cites>FETCH-LOGICAL-c470t-5aed96a9ec75f48a35da438641a5db9553329f0f013567cbf7682c49f62a28d73</cites><orcidid>0000-0001-8359-6599</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,782,786,887,27931,27932</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30710115$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Di Costanzo, Alessia</creatorcontrib><creatorcontrib>Pacifico, Lucia</creatorcontrib><creatorcontrib>Chiesa, Claudio</creatorcontrib><creatorcontrib>Perla, Francesco Massimo</creatorcontrib><creatorcontrib>Ceci, Fabrizio</creatorcontrib><creatorcontrib>Angeloni, Antonio</creatorcontrib><creatorcontrib>D’Erasmo, Laura</creatorcontrib><creatorcontrib>Di Martino, Michele</creatorcontrib><creatorcontrib>Arca, Marcello</creatorcontrib><title>Genetic and metabolic predictors of hepatic fat content in a cohort of Italian children with obesity</title><title>Pediatric research</title><addtitle>Pediatr Res</addtitle><addtitle>Pediatr Res</addtitle><description>Objectives
To comprehensively explore metabolic and genetic contributors to liver fat accumulation in overweight/obese children.
Methods
Two hundred thirty Italian children with obesity were investigated for metabolic parameters and genotyped for
PNPLA3
,
TM6SF2
,
GCKR
, and
MBOAT7
gene variants. Percentage hepatic fat content (HFF%) was measured by nuclear magnetic resonance.
Results
HFF% was positively related with BMI, HOMA
IR
, metabolic syndrome, ALT, AST, γGT, and albumin. Carriers of [G] allele in
PNPLA3
, [T] allele in
GCKR
and [T] allele in
TM6SF2
genes had significantly higher hepatic fat content than wild-type carriers. HFF% was explained for 8.7% by metabolic and for 16.1% by genetic factors and, a model including age, gender, BMI, HOMA
IR
,
PNPLA3
,
GCKR
, and
TM6SF2
variants was the best predictor of HFF%, explaining 24.8% of its variation (
P
< 0.001). A weighted-genetic risk score combining
PNPLA3
,
GCKR,
and
TM6SF2
risk alleles was associated with almost eightfold higher risk of NAFLD.
Conclusions
Our data highlighted the predominant role of genetic factors in determining the amount of liver fat content in children with obesity.</description><subject>Acyltransferases - genetics</subject><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adipose Tissue - metabolism</subject><subject>Adolescent</subject><subject>Alleles</subject><subject>Body Mass Index</subject><subject>Child</subject><subject>Clinical</subject><subject>Clinical Research Article</subject><subject>DNA - analysis</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic Variation</subject><subject>Genotype</subject><subject>Humans</subject><subject>Italy - epidemiology</subject><subject>Lipase - genetics</subject><subject>Liver - diagnostic imaging</subject><subject>Liver - pathology</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Membrane Proteins - genetics</subject><subject>Metabolism</subject><subject>Non-alcoholic Fatty Liver Disease - diagnostic imaging</subject><subject>Non-alcoholic Fatty Liver Disease - genetics</subject><subject>Obesity</subject><subject>Overweight</subject><subject>Pediatric Obesity - epidemiology</subject><subject>Pediatric Obesity - genetics</subject><subject>Pediatric Surgery</subject><subject>Pediatrics</subject><subject>Risk</subject><issn>0031-3998</issn><issn>1530-0447</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kU1vFDEMhiMEotvCD-CCInHhMmBPkklyQUIVtJUqcYFzlMlkOqlmkyXJUvXfk9WW8iFxsmw_fm3rJeQVwjsEpt4XjkxDB6g7YMA6fEI2KFircC6fkg0Aw45prU7IaSm3AMiF4s_JCQOJgCg2ZLrw0dfgqI0T3fpqx7S2bJf9FFxNudA008Xv7IGZbaUuxepjpSFS25Il5XpArqpdg43ULWGdso_0LtSFptGXUO9fkGezXYt_-RDPyLfPn76eX3bXXy6uzj9ed45LqJ2wftKD1d5JMXNlmZgsZ2rgaMU0aiEY6_UMMyATg3TjLAfVO67nobe9miQ7Ix-Ourv9uPWTa3dmu5pdDlub702ywfzdiWExN-mHGeQAYoAm8PZBIKfve1-q2Ybi_Lra6NO-mB6lFgBtbUPf_IPepn2O7b1GacmwV6gahUfK5VRK9vPjMQjm4KE5emiah-bgocE28_rPLx4nfpnWgP4IlNaKNz7_Xv1_1Z-byKeJ</recordid><startdate>20190401</startdate><enddate>20190401</enddate><creator>Di Costanzo, Alessia</creator><creator>Pacifico, Lucia</creator><creator>Chiesa, Claudio</creator><creator>Perla, Francesco Massimo</creator><creator>Ceci, Fabrizio</creator><creator>Angeloni, Antonio</creator><creator>D’Erasmo, Laura</creator><creator>Di Martino, Michele</creator><creator>Arca, Marcello</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8359-6599</orcidid></search><sort><creationdate>20190401</creationdate><title>Genetic and metabolic predictors of hepatic fat content in a cohort of Italian children with obesity</title><author>Di Costanzo, Alessia ; Pacifico, Lucia ; Chiesa, Claudio ; Perla, Francesco Massimo ; Ceci, Fabrizio ; Angeloni, Antonio ; D’Erasmo, Laura ; Di Martino, Michele ; Arca, Marcello</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-5aed96a9ec75f48a35da438641a5db9553329f0f013567cbf7682c49f62a28d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Acyltransferases - genetics</topic><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Adipose Tissue - metabolism</topic><topic>Adolescent</topic><topic>Alleles</topic><topic>Body Mass Index</topic><topic>Child</topic><topic>Clinical</topic><topic>Clinical Research Article</topic><topic>DNA - analysis</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic Variation</topic><topic>Genotype</topic><topic>Humans</topic><topic>Italy - epidemiology</topic><topic>Lipase - genetics</topic><topic>Liver - diagnostic imaging</topic><topic>Liver - pathology</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Membrane Proteins - genetics</topic><topic>Metabolism</topic><topic>Non-alcoholic Fatty Liver Disease - diagnostic imaging</topic><topic>Non-alcoholic Fatty Liver Disease - genetics</topic><topic>Obesity</topic><topic>Overweight</topic><topic>Pediatric Obesity - epidemiology</topic><topic>Pediatric Obesity - genetics</topic><topic>Pediatric Surgery</topic><topic>Pediatrics</topic><topic>Risk</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Di Costanzo, Alessia</creatorcontrib><creatorcontrib>Pacifico, Lucia</creatorcontrib><creatorcontrib>Chiesa, Claudio</creatorcontrib><creatorcontrib>Perla, Francesco Massimo</creatorcontrib><creatorcontrib>Ceci, Fabrizio</creatorcontrib><creatorcontrib>Angeloni, Antonio</creatorcontrib><creatorcontrib>D’Erasmo, Laura</creatorcontrib><creatorcontrib>Di Martino, Michele</creatorcontrib><creatorcontrib>Arca, Marcello</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pediatric research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Di Costanzo, Alessia</au><au>Pacifico, Lucia</au><au>Chiesa, Claudio</au><au>Perla, Francesco Massimo</au><au>Ceci, Fabrizio</au><au>Angeloni, Antonio</au><au>D’Erasmo, Laura</au><au>Di Martino, Michele</au><au>Arca, Marcello</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic and metabolic predictors of hepatic fat content in a cohort of Italian children with obesity</atitle><jtitle>Pediatric research</jtitle><stitle>Pediatr Res</stitle><addtitle>Pediatr Res</addtitle><date>2019-04-01</date><risdate>2019</risdate><volume>85</volume><issue>5</issue><spage>671</spage><epage>677</epage><pages>671-677</pages><issn>0031-3998</issn><eissn>1530-0447</eissn><abstract>Objectives
To comprehensively explore metabolic and genetic contributors to liver fat accumulation in overweight/obese children.
Methods
Two hundred thirty Italian children with obesity were investigated for metabolic parameters and genotyped for
PNPLA3
,
TM6SF2
,
GCKR
, and
MBOAT7
gene variants. Percentage hepatic fat content (HFF%) was measured by nuclear magnetic resonance.
Results
HFF% was positively related with BMI, HOMA
IR
, metabolic syndrome, ALT, AST, γGT, and albumin. Carriers of [G] allele in
PNPLA3
, [T] allele in
GCKR
and [T] allele in
TM6SF2
genes had significantly higher hepatic fat content than wild-type carriers. HFF% was explained for 8.7% by metabolic and for 16.1% by genetic factors and, a model including age, gender, BMI, HOMA
IR
,
PNPLA3
,
GCKR
, and
TM6SF2
variants was the best predictor of HFF%, explaining 24.8% of its variation (
P
< 0.001). A weighted-genetic risk score combining
PNPLA3
,
GCKR,
and
TM6SF2
risk alleles was associated with almost eightfold higher risk of NAFLD.
Conclusions
Our data highlighted the predominant role of genetic factors in determining the amount of liver fat content in children with obesity.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>30710115</pmid><doi>10.1038/s41390-019-0303-1</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-8359-6599</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0031-3998 |
| ispartof | Pediatric research, 2019-04, Vol.85 (5), p.671-677 |
| issn | 0031-3998 1530-0447 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6760560 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Acyltransferases - genetics Adaptor Proteins, Signal Transducing - genetics Adipose Tissue - metabolism Adolescent Alleles Body Mass Index Child Clinical Clinical Research Article DNA - analysis Female Genetic Predisposition to Disease Genetic Variation Genotype Humans Italy - epidemiology Lipase - genetics Liver - diagnostic imaging Liver - pathology Magnetic Resonance Spectroscopy Male Medicine Medicine & Public Health Membrane Proteins - genetics Metabolism Non-alcoholic Fatty Liver Disease - diagnostic imaging Non-alcoholic Fatty Liver Disease - genetics Obesity Overweight Pediatric Obesity - epidemiology Pediatric Obesity - genetics Pediatric Surgery Pediatrics Risk |
| title | Genetic and metabolic predictors of hepatic fat content in a cohort of Italian children with obesity |
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