The role of mitochondrial genomics in patients with non-alcoholic steatohepatitis (NASH)
Visceral obesity and metabolic syndrome are commonly associated with non-alcoholic fatty liver disease (NAFLD). The progression of steatosis to NASH depends on a number of metabolic and patient-related factors. The mechanisms of genetic predisposition towards the development of NASH and related fibr...
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| Veröffentlicht in: | BMC medical genetics 2016-09, Vol.17 (1), p.63-63, Article 63 |
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| creator | Mehta, Rohini Jeiran, Kianoush Koenig, Aaron B Otgonsuren, Munkzhul Goodman, Zachary Baranova, Ancha Younossi, Zobair |
| description | Visceral obesity and metabolic syndrome are commonly associated with non-alcoholic fatty liver disease (NAFLD). The progression of steatosis to NASH depends on a number of metabolic and patient-related factors. The mechanisms of genetic predisposition towards the development of NASH and related fibrosis remain unclear. In this study, our aim was to utilize mitotyping and identify mitochondrial haplotypes that may be associated with NAFLD.
We examined mitochondrial haplotypes along with patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 genotype to determine their association with NAFLD phenotypes. Whole blood samples were obtained from 341 patients (BMI > 35) undergoing weight reduction surgery after written consent. Liver biopsies were centrally reviewed by a single pathologist based on predetermined pathologic protocol (41.9 % Non-NASH NAFLD, 30.4 % NASH, 27.5 % controls). A 1,122 bp of the mitochondrial control loop was sequenced for each sample and classified into haplogroups.
The presence of haplogroup L exhibits protection against the development of NASH and pericellular fibrosis. The alleles of PNPLA3 locus showed differential distribution in cohorts with NAFLD, NASH and pericellular fibrosis. Heterozygosity at this locus is independently associated with higher risk of having NASH and pericellular fibrosis.
Mitochondrial genetics play an important role in NASH probably by modulation of oxidative stress and the efficiency of oxidative phosphorylation. |
| doi_str_mv | 10.1186/s12881-016-0324-0 |
| format | Article |
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We examined mitochondrial haplotypes along with patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 genotype to determine their association with NAFLD phenotypes. Whole blood samples were obtained from 341 patients (BMI > 35) undergoing weight reduction surgery after written consent. Liver biopsies were centrally reviewed by a single pathologist based on predetermined pathologic protocol (41.9 % Non-NASH NAFLD, 30.4 % NASH, 27.5 % controls). A 1,122 bp of the mitochondrial control loop was sequenced for each sample and classified into haplogroups.
The presence of haplogroup L exhibits protection against the development of NASH and pericellular fibrosis. The alleles of PNPLA3 locus showed differential distribution in cohorts with NAFLD, NASH and pericellular fibrosis. Heterozygosity at this locus is independently associated with higher risk of having NASH and pericellular fibrosis.
Mitochondrial genetics play an important role in NASH probably by modulation of oxidative stress and the efficiency of oxidative phosphorylation.</description><identifier>ISSN: 1471-2350</identifier><identifier>EISSN: 1471-2350</identifier><identifier>DOI: 10.1186/s12881-016-0324-0</identifier><identifier>PMID: 27596100</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adult ; Analysis ; Biopsy ; Body mass index ; Complications and side effects ; Fatty liver ; Female ; Genetic Predisposition to Disease ; Genetic testing ; Genome, Mitochondrial ; Genomics ; Genomics - methods ; Haplotypes ; Humans ; Hypotheses ; Inflammation ; Lipase - genetics ; Liver - pathology ; Liver cancer ; Liver diseases ; Male ; Membrane Proteins - genetics ; Metabolic syndrome ; Metabolic syndrome X ; Metabolites ; Middle Aged ; Mitochondria - genetics ; Mutation ; Non-alcoholic Fatty Liver Disease - genetics ; Non-alcoholic Fatty Liver Disease - pathology ; Obesity ; Patients ; Polymorphism, Single Nucleotide ; Proteins ; Sequence Analysis, DNA - methods ; Thermal cycling ; Triglycerides</subject><ispartof>BMC medical genetics, 2016-09, Vol.17 (1), p.63-63, Article 63</ispartof><rights>COPYRIGHT 2016 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2016</rights><rights>The Author(s). 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c528t-6a69dc29f542acd6deac878d42fb7af255fcc96bfbac8ea82900dd8a843111393</citedby><cites>FETCH-LOGICAL-c528t-6a69dc29f542acd6deac878d42fb7af255fcc96bfbac8ea82900dd8a843111393</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011877/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011877/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27596100$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mehta, Rohini</creatorcontrib><creatorcontrib>Jeiran, Kianoush</creatorcontrib><creatorcontrib>Koenig, Aaron B</creatorcontrib><creatorcontrib>Otgonsuren, Munkzhul</creatorcontrib><creatorcontrib>Goodman, Zachary</creatorcontrib><creatorcontrib>Baranova, Ancha</creatorcontrib><creatorcontrib>Younossi, Zobair</creatorcontrib><title>The role of mitochondrial genomics in patients with non-alcoholic steatohepatitis (NASH)</title><title>BMC medical genetics</title><addtitle>BMC Med Genet</addtitle><description>Visceral obesity and metabolic syndrome are commonly associated with non-alcoholic fatty liver disease (NAFLD). The progression of steatosis to NASH depends on a number of metabolic and patient-related factors. The mechanisms of genetic predisposition towards the development of NASH and related fibrosis remain unclear. In this study, our aim was to utilize mitotyping and identify mitochondrial haplotypes that may be associated with NAFLD.
We examined mitochondrial haplotypes along with patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 genotype to determine their association with NAFLD phenotypes. Whole blood samples were obtained from 341 patients (BMI > 35) undergoing weight reduction surgery after written consent. Liver biopsies were centrally reviewed by a single pathologist based on predetermined pathologic protocol (41.9 % Non-NASH NAFLD, 30.4 % NASH, 27.5 % controls). A 1,122 bp of the mitochondrial control loop was sequenced for each sample and classified into haplogroups.
The presence of haplogroup L exhibits protection against the development of NASH and pericellular fibrosis. The alleles of PNPLA3 locus showed differential distribution in cohorts with NAFLD, NASH and pericellular fibrosis. Heterozygosity at this locus is independently associated with higher risk of having NASH and pericellular fibrosis.
Mitochondrial genetics play an important role in NASH probably by modulation of oxidative stress and the efficiency of oxidative phosphorylation.</description><subject>Adult</subject><subject>Analysis</subject><subject>Biopsy</subject><subject>Body mass index</subject><subject>Complications and side effects</subject><subject>Fatty liver</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic testing</subject><subject>Genome, Mitochondrial</subject><subject>Genomics</subject><subject>Genomics - methods</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Inflammation</subject><subject>Lipase - genetics</subject><subject>Liver - pathology</subject><subject>Liver cancer</subject><subject>Liver diseases</subject><subject>Male</subject><subject>Membrane Proteins - genetics</subject><subject>Metabolic syndrome</subject><subject>Metabolic syndrome X</subject><subject>Metabolites</subject><subject>Middle Aged</subject><subject>Mitochondria - genetics</subject><subject>Mutation</subject><subject>Non-alcoholic Fatty Liver Disease - genetics</subject><subject>Non-alcoholic Fatty Liver Disease - pathology</subject><subject>Obesity</subject><subject>Patients</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Proteins</subject><subject>Sequence Analysis, DNA - methods</subject><subject>Thermal cycling</subject><subject>Triglycerides</subject><issn>1471-2350</issn><issn>1471-2350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkl1rHCEYhaW0NMm2P6A3RehNcjGpOqPj3BSW0DSB0EKTQu_E9WPH4OhWnbT993XZdMmWIqi8Pu9RDweANxidY8zZ-4wJ57hBmDWoJV2DnoFj3PW4IS1Fz5_sj8BJzvcI4Z637UtwRHo6MIzQMfh-NxqYojcwWji5EtUYg05Oerg2IU5OZegC3MjiTCgZ_nRlhCGGRnoVx-idgrkYWeJotkxxGZ5-Xt5enb0CL6z02bx-XBfg2-XHu4ur5ubLp-uL5U2jKOGlYZINWpHB0o5IpZk2UvGe647YVS8todQqNbCVXdW6kZwMCGnNJe9ajHE7tAvwYae7mVeT0aq-MkkvNslNMv0WUTpxeBLcKNbxQVBUPez7KnD6KJDij9nkIiaXlfFeBhPnLDDHPWWYElrRd_-g93FOoX6vUqQKElbftKfW0hvhgo31XrUVFcuODQOnlavU-X-oOrSppsdgrKv1g4azg4bKFPOrrOWcs7i-_XrI4h2rUsw5Gbv3AyOxjY7YRUfU6IhtdOq0AG-fGrnv-JuV9g87Ub3M</recordid><startdate>20160905</startdate><enddate>20160905</enddate><creator>Mehta, Rohini</creator><creator>Jeiran, Kianoush</creator><creator>Koenig, Aaron B</creator><creator>Otgonsuren, Munkzhul</creator><creator>Goodman, Zachary</creator><creator>Baranova, Ancha</creator><creator>Younossi, Zobair</creator><general>BioMed Central Ltd</general><general>BioMed Central</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>ISR</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160905</creationdate><title>The role of mitochondrial genomics in patients with non-alcoholic steatohepatitis (NASH)</title><author>Mehta, Rohini ; Jeiran, Kianoush ; Koenig, Aaron B ; Otgonsuren, Munkzhul ; Goodman, Zachary ; Baranova, Ancha ; Younossi, Zobair</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c528t-6a69dc29f542acd6deac878d42fb7af255fcc96bfbac8ea82900dd8a843111393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Analysis</topic><topic>Biopsy</topic><topic>Body mass index</topic><topic>Complications and side effects</topic><topic>Fatty liver</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic testing</topic><topic>Genome, Mitochondrial</topic><topic>Genomics</topic><topic>Genomics - methods</topic><topic>Haplotypes</topic><topic>Humans</topic><topic>Hypotheses</topic><topic>Inflammation</topic><topic>Lipase - genetics</topic><topic>Liver - pathology</topic><topic>Liver cancer</topic><topic>Liver diseases</topic><topic>Male</topic><topic>Membrane Proteins - genetics</topic><topic>Metabolic syndrome</topic><topic>Metabolic syndrome X</topic><topic>Metabolites</topic><topic>Middle Aged</topic><topic>Mitochondria - genetics</topic><topic>Mutation</topic><topic>Non-alcoholic Fatty Liver Disease - genetics</topic><topic>Non-alcoholic Fatty Liver Disease - pathology</topic><topic>Obesity</topic><topic>Patients</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Proteins</topic><topic>Sequence Analysis, DNA - methods</topic><topic>Thermal cycling</topic><topic>Triglycerides</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mehta, Rohini</creatorcontrib><creatorcontrib>Jeiran, Kianoush</creatorcontrib><creatorcontrib>Koenig, Aaron B</creatorcontrib><creatorcontrib>Otgonsuren, Munkzhul</creatorcontrib><creatorcontrib>Goodman, Zachary</creatorcontrib><creatorcontrib>Baranova, Ancha</creatorcontrib><creatorcontrib>Younossi, Zobair</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</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>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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 Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content 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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BMC medical genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mehta, Rohini</au><au>Jeiran, Kianoush</au><au>Koenig, Aaron B</au><au>Otgonsuren, Munkzhul</au><au>Goodman, Zachary</au><au>Baranova, Ancha</au><au>Younossi, Zobair</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of mitochondrial genomics in patients with non-alcoholic steatohepatitis (NASH)</atitle><jtitle>BMC medical genetics</jtitle><addtitle>BMC Med Genet</addtitle><date>2016-09-05</date><risdate>2016</risdate><volume>17</volume><issue>1</issue><spage>63</spage><epage>63</epage><pages>63-63</pages><artnum>63</artnum><issn>1471-2350</issn><eissn>1471-2350</eissn><abstract>Visceral obesity and metabolic syndrome are commonly associated with non-alcoholic fatty liver disease (NAFLD). The progression of steatosis to NASH depends on a number of metabolic and patient-related factors. The mechanisms of genetic predisposition towards the development of NASH and related fibrosis remain unclear. In this study, our aim was to utilize mitotyping and identify mitochondrial haplotypes that may be associated with NAFLD.
We examined mitochondrial haplotypes along with patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 genotype to determine their association with NAFLD phenotypes. Whole blood samples were obtained from 341 patients (BMI > 35) undergoing weight reduction surgery after written consent. Liver biopsies were centrally reviewed by a single pathologist based on predetermined pathologic protocol (41.9 % Non-NASH NAFLD, 30.4 % NASH, 27.5 % controls). A 1,122 bp of the mitochondrial control loop was sequenced for each sample and classified into haplogroups.
The presence of haplogroup L exhibits protection against the development of NASH and pericellular fibrosis. The alleles of PNPLA3 locus showed differential distribution in cohorts with NAFLD, NASH and pericellular fibrosis. Heterozygosity at this locus is independently associated with higher risk of having NASH and pericellular fibrosis.
Mitochondrial genetics play an important role in NASH probably by modulation of oxidative stress and the efficiency of oxidative phosphorylation.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>27596100</pmid><doi>10.1186/s12881-016-0324-0</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Analysis Biopsy Body mass index Complications and side effects Fatty liver Female Genetic Predisposition to Disease Genetic testing Genome, Mitochondrial Genomics Genomics - methods Haplotypes Humans Hypotheses Inflammation Lipase - genetics Liver - pathology Liver cancer Liver diseases Male Membrane Proteins - genetics Metabolic syndrome Metabolic syndrome X Metabolites Middle Aged Mitochondria - genetics Mutation Non-alcoholic Fatty Liver Disease - genetics Non-alcoholic Fatty Liver Disease - pathology Obesity Patients Polymorphism, Single Nucleotide Proteins Sequence Analysis, DNA - methods Thermal cycling Triglycerides |
| title | The role of mitochondrial genomics in patients with non-alcoholic steatohepatitis (NASH) |
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