Association of MTTP gene variants with pediatric NAFLD: A candidate-gene-based analysis of single nucleotide variations in obese children
We used targeted next-generation sequencing to investigate whether genetic variants of lipid metabolism-related genes are associated with increased susceptibility to nonalcoholic fatty liver disease (NAFLD) in obese children. A cohort of 100 obese children aged 6 to 18 years were divided into NAFLD...
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| creator | Dai, Dongling Wen, Feiqiu Zhou, Shaoming Su, Zhe Liu, Guosheng Wang, Mingbang Zhou, Jianli He, Fusheng |
| description | We used targeted next-generation sequencing to investigate whether genetic variants of lipid metabolism-related genes are associated with increased susceptibility to nonalcoholic fatty liver disease (NAFLD) in obese children.
A cohort of 100 obese children aged 6 to 18 years were divided into NAFLD and non-NAFLD groups and subjected to hepatic ultrasound, anthropometric, and biochemical analyses. We evaluated the association of genetic variants with NAFLD susceptibility by investigating the single nucleotide polymorphisms in each of 36 lipid-metabolism-related genes. The panel genes were assembled for target region sequencing. Correlations between single nucleotide variations, biochemical markers, and clinical phenotypes were analyzed.
97 variants in the 36 target genes per child were uncovered. Twenty-six variants in 16 genes were more prevalent in NAFLD subjects than in in-house controls. The mutation rate of MTTP rs2306986 and SLC6A2 rs3743788 was significantly higher in NAFLD subjects than in non-NAFLD subjects (OR: 3.879; P = 0.004; OR: 6.667, P = 0.005). Logistic regression analysis indicated the MTTP variant rs2306986 was an independent risk factor for NAFLD (OR: 23.468, P = 0.044).
The results of this study, examining a cohort of obese children, suggest that the genetic variation at MTTP rs2306986 was associated with higher susceptibility to NAFLD. This may contribute to the altered lipid metabolism by disruption of assembly and secretion of lipoprotein, leading to reducing fat export from the involved hepatocytes. |
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A cohort of 100 obese children aged 6 to 18 years were divided into NAFLD and non-NAFLD groups and subjected to hepatic ultrasound, anthropometric, and biochemical analyses. We evaluated the association of genetic variants with NAFLD susceptibility by investigating the single nucleotide polymorphisms in each of 36 lipid-metabolism-related genes. The panel genes were assembled for target region sequencing. Correlations between single nucleotide variations, biochemical markers, and clinical phenotypes were analyzed.
97 variants in the 36 target genes per child were uncovered. Twenty-six variants in 16 genes were more prevalent in NAFLD subjects than in in-house controls. The mutation rate of MTTP rs2306986 and SLC6A2 rs3743788 was significantly higher in NAFLD subjects than in non-NAFLD subjects (OR: 3.879; P = 0.004; OR: 6.667, P = 0.005). Logistic regression analysis indicated the MTTP variant rs2306986 was an independent risk factor for NAFLD (OR: 23.468, P = 0.044).
The results of this study, examining a cohort of obese children, suggest that the genetic variation at MTTP rs2306986 was associated with higher susceptibility to NAFLD. This may contribute to the altered lipid metabolism by disruption of assembly and secretion of lipoprotein, leading to reducing fat export from the involved hepatocytes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0185396</identifier><identifier>PMID: 28953935</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Anthropometry ; Apolipoproteins ; Biochemical markers ; Biology and Life Sciences ; Carrier Proteins - genetics ; Child ; Childhood obesity ; Children ; Children & youth ; Cholesterol ; Cohort Studies ; Complications and side effects ; Disruption ; Fasting ; Fatty liver ; Female ; Gene expression ; Gene sequencing ; Genes ; Genetic aspects ; Genetic diversity ; Genetic variation ; Hepatocytes ; Hepatology ; Hospitals ; Humans ; Insulin resistance ; Laboratories ; Lipid metabolism ; Lipids ; Liver ; Liver diseases ; Male ; Medical research ; Medicine and Health Sciences ; Mental depression ; Metabolism ; Mutation ; NMR ; Non-alcoholic Fatty Liver Disease - complications ; Non-alcoholic Fatty Liver Disease - genetics ; Nuclear magnetic resonance ; Obesity ; Obesity - complications ; Obesity - genetics ; Pediatrics ; People and places ; Physiological aspects ; Polymorphism, Single Nucleotide ; Proteins ; Regression analysis ; Risk factors ; Secretion ; Single-nucleotide polymorphism ; Studies ; Ultrasonic imaging ; Ultrasound</subject><ispartof>PloS one, 2017-09, Vol.12 (9), p.e0185396-e0185396</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Dai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Dai et al 2017 Dai et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-3cc5cb9b7dce4075f7a9417b1e61933ed8fe9da5f2e1ec26b2992844ac992d713</citedby><cites>FETCH-LOGICAL-c692t-3cc5cb9b7dce4075f7a9417b1e61933ed8fe9da5f2e1ec26b2992844ac992d713</cites><orcidid>0000-0001-6555-3210</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617203/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617203/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28953935$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Baroni, Marco Giorgio</contributor><creatorcontrib>Dai, Dongling</creatorcontrib><creatorcontrib>Wen, Feiqiu</creatorcontrib><creatorcontrib>Zhou, Shaoming</creatorcontrib><creatorcontrib>Su, Zhe</creatorcontrib><creatorcontrib>Liu, Guosheng</creatorcontrib><creatorcontrib>Wang, Mingbang</creatorcontrib><creatorcontrib>Zhou, Jianli</creatorcontrib><creatorcontrib>He, Fusheng</creatorcontrib><title>Association of MTTP gene variants with pediatric NAFLD: A candidate-gene-based analysis of single nucleotide variations in obese children</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>We used targeted next-generation sequencing to investigate whether genetic variants of lipid metabolism-related genes are associated with increased susceptibility to nonalcoholic fatty liver disease (NAFLD) in obese children.
A cohort of 100 obese children aged 6 to 18 years were divided into NAFLD and non-NAFLD groups and subjected to hepatic ultrasound, anthropometric, and biochemical analyses. We evaluated the association of genetic variants with NAFLD susceptibility by investigating the single nucleotide polymorphisms in each of 36 lipid-metabolism-related genes. The panel genes were assembled for target region sequencing. Correlations between single nucleotide variations, biochemical markers, and clinical phenotypes were analyzed.
97 variants in the 36 target genes per child were uncovered. Twenty-six variants in 16 genes were more prevalent in NAFLD subjects than in in-house controls. The mutation rate of MTTP rs2306986 and SLC6A2 rs3743788 was significantly higher in NAFLD subjects than in non-NAFLD subjects (OR: 3.879; P = 0.004; OR: 6.667, P = 0.005). Logistic regression analysis indicated the MTTP variant rs2306986 was an independent risk factor for NAFLD (OR: 23.468, P = 0.044).
The results of this study, examining a cohort of obese children, suggest that the genetic variation at MTTP rs2306986 was associated with higher susceptibility to NAFLD. This may contribute to the altered lipid metabolism by disruption of assembly and secretion of lipoprotein, leading to reducing fat export from the involved hepatocytes.</description><subject>Adolescent</subject><subject>Anthropometry</subject><subject>Apolipoproteins</subject><subject>Biochemical markers</subject><subject>Biology and Life Sciences</subject><subject>Carrier Proteins - genetics</subject><subject>Child</subject><subject>Childhood obesity</subject><subject>Children</subject><subject>Children & youth</subject><subject>Cholesterol</subject><subject>Cohort Studies</subject><subject>Complications and side effects</subject><subject>Disruption</subject><subject>Fasting</subject><subject>Fatty liver</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic variation</subject><subject>Hepatocytes</subject><subject>Hepatology</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Insulin resistance</subject><subject>Laboratories</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Liver</subject><subject>Liver diseases</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Mental depression</subject><subject>Metabolism</subject><subject>Mutation</subject><subject>NMR</subject><subject>Non-alcoholic Fatty Liver Disease - complications</subject><subject>Non-alcoholic Fatty Liver Disease - genetics</subject><subject>Nuclear magnetic resonance</subject><subject>Obesity</subject><subject>Obesity - complications</subject><subject>Obesity - genetics</subject><subject>Pediatrics</subject><subject>People and places</subject><subject>Physiological aspects</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Proteins</subject><subject>Regression analysis</subject><subject>Risk factors</subject><subject>Secretion</subject><subject>Single-nucleotide polymorphism</subject><subject>Studies</subject><subject>Ultrasonic imaging</subject><subject>Ultrasound</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk91u0zAUxyMEYmPwBggsISG4SInjJE52gVQNBpUKQ1C4tRz7JPWU2sV2BnsE3hqnzaYG7QLlwtHx7_zPl08UPcXJDBOK31ya3mrezbZGwyzBZU6q4l50jCuSxkWakPsH_0fRI-cukyQnZVE8jI7Ssgo4yY-jP3PnjFDcK6ORadCn1eoLakEDuuJWce0d-qX8Gm1BBsgqgT7Pz5fvTtEcCa6lktxDPPBxzR1IxENK1065Qcsp3XaAdC86MF7JUXMI5ZAK4WpwgMRaddKCfhw9aHjn4Ml4nkTfz9-vzj7Gy4sPi7P5MhZFlfqYCJGLuqqpFJAlNG8orzJMawxFKJeALBuoJM-bFDCItKjTqkrLLOMinJJichI93-tuO-PY2EXHcJWRoJCXSSAWe0Iafsm2Vm24vWaGK7YzGNsybr0KVTGooYI8gVSmOCsBOJRYEFonsklpMAett2O0vt5AyFl7y7uJ6PRGqzVrzRXLC0zD5ILAq1HAmp89OM82ygnoOq7B9Lu8syzMEpcBffEPend1I9XyUIDSjQlxxSDK5nlSlJTm2ZD37A4qfBI2SoQn16hgnzi8njgExsNv3_LeObb49vX_2YsfU_blAbsG3vm1M12_e0VTMNuDwhrnLDS3TcYJGzbmphts2Bg2bkxwe3Y4oFunmxUhfwGdfhJx</recordid><startdate>20170927</startdate><enddate>20170927</enddate><creator>Dai, Dongling</creator><creator>Wen, Feiqiu</creator><creator>Zhou, Shaoming</creator><creator>Su, Zhe</creator><creator>Liu, Guosheng</creator><creator>Wang, Mingbang</creator><creator>Zhou, Jianli</creator><creator>He, Fusheng</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-6555-3210</orcidid></search><sort><creationdate>20170927</creationdate><title>Association of MTTP gene variants with pediatric NAFLD: A candidate-gene-based analysis of single nucleotide variations in obese children</title><author>Dai, Dongling ; Wen, Feiqiu ; Zhou, Shaoming ; Su, Zhe ; Liu, Guosheng ; Wang, Mingbang ; Zhou, Jianli ; He, Fusheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-3cc5cb9b7dce4075f7a9417b1e61933ed8fe9da5f2e1ec26b2992844ac992d713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adolescent</topic><topic>Anthropometry</topic><topic>Apolipoproteins</topic><topic>Biochemical markers</topic><topic>Biology and Life Sciences</topic><topic>Carrier Proteins - genetics</topic><topic>Child</topic><topic>Childhood obesity</topic><topic>Children</topic><topic>Children & youth</topic><topic>Cholesterol</topic><topic>Cohort Studies</topic><topic>Complications and side effects</topic><topic>Disruption</topic><topic>Fasting</topic><topic>Fatty liver</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene sequencing</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genetic variation</topic><topic>Hepatocytes</topic><topic>Hepatology</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Insulin resistance</topic><topic>Laboratories</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>Liver</topic><topic>Liver diseases</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Mental depression</topic><topic>Metabolism</topic><topic>Mutation</topic><topic>NMR</topic><topic>Non-alcoholic Fatty Liver Disease - complications</topic><topic>Non-alcoholic Fatty Liver Disease - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dai, Dongling</au><au>Wen, Feiqiu</au><au>Zhou, Shaoming</au><au>Su, Zhe</au><au>Liu, Guosheng</au><au>Wang, Mingbang</au><au>Zhou, Jianli</au><au>He, Fusheng</au><au>Baroni, Marco Giorgio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of MTTP gene variants with pediatric NAFLD: A candidate-gene-based analysis of single nucleotide variations in obese children</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-09-27</date><risdate>2017</risdate><volume>12</volume><issue>9</issue><spage>e0185396</spage><epage>e0185396</epage><pages>e0185396-e0185396</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>We used targeted next-generation sequencing to investigate whether genetic variants of lipid metabolism-related genes are associated with increased susceptibility to nonalcoholic fatty liver disease (NAFLD) in obese children.
A cohort of 100 obese children aged 6 to 18 years were divided into NAFLD and non-NAFLD groups and subjected to hepatic ultrasound, anthropometric, and biochemical analyses. We evaluated the association of genetic variants with NAFLD susceptibility by investigating the single nucleotide polymorphisms in each of 36 lipid-metabolism-related genes. The panel genes were assembled for target region sequencing. Correlations between single nucleotide variations, biochemical markers, and clinical phenotypes were analyzed.
97 variants in the 36 target genes per child were uncovered. Twenty-six variants in 16 genes were more prevalent in NAFLD subjects than in in-house controls. The mutation rate of MTTP rs2306986 and SLC6A2 rs3743788 was significantly higher in NAFLD subjects than in non-NAFLD subjects (OR: 3.879; P = 0.004; OR: 6.667, P = 0.005). Logistic regression analysis indicated the MTTP variant rs2306986 was an independent risk factor for NAFLD (OR: 23.468, P = 0.044).
The results of this study, examining a cohort of obese children, suggest that the genetic variation at MTTP rs2306986 was associated with higher susceptibility to NAFLD. This may contribute to the altered lipid metabolism by disruption of assembly and secretion of lipoprotein, leading to reducing fat export from the involved hepatocytes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28953935</pmid><doi>10.1371/journal.pone.0185396</doi><tpages>e0185396</tpages><orcidid>https://orcid.org/0000-0001-6555-3210</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-09, Vol.12 (9), p.e0185396-e0185396 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1943619580 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adolescent Anthropometry Apolipoproteins Biochemical markers Biology and Life Sciences Carrier Proteins - genetics Child Childhood obesity Children Children & youth Cholesterol Cohort Studies Complications and side effects Disruption Fasting Fatty liver Female Gene expression Gene sequencing Genes Genetic aspects Genetic diversity Genetic variation Hepatocytes Hepatology Hospitals Humans Insulin resistance Laboratories Lipid metabolism Lipids Liver Liver diseases Male Medical research Medicine and Health Sciences Mental depression Metabolism Mutation NMR Non-alcoholic Fatty Liver Disease - complications Non-alcoholic Fatty Liver Disease - genetics Nuclear magnetic resonance Obesity Obesity - complications Obesity - genetics Pediatrics People and places Physiological aspects Polymorphism, Single Nucleotide Proteins Regression analysis Risk factors Secretion Single-nucleotide polymorphism Studies Ultrasonic imaging Ultrasound |
| title | Association of MTTP gene variants with pediatric NAFLD: A candidate-gene-based analysis of single nucleotide variations in obese children |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T03%3A21%3A10IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Association%20of%20MTTP%20gene%20variants%20with%20pediatric%20NAFLD:%20A%20candidate-gene-based%20analysis%20of%20single%20nucleotide%20variations%20in%20obese%20children&rft.jtitle=PloS%20one&rft.au=Dai,%20Dongling&rft.date=2017-09-27&rft.volume=12&rft.issue=9&rft.spage=e0185396&rft.epage=e0185396&rft.pages=e0185396-e0185396&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0185396&rft_dat=%3Cgale_plos_%3EA506877542%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1943619580&rft_id=info:pmid/28953935&rft_galeid=A506877542&rft_doaj_id=oai_doaj_org_article_ebe9e50e2d2148eeae81c37b0df270e2&rfr_iscdi=true |