Differential DNA methylation of MSI2 and its correlation with diabetic traits
Differential DNA methylation with hyperglycemia is significantly associated with Type 2 Diabetes (T2D). Longtime extended exposure to high blood glucose levels can affect the epigenetic signatures in all organs. However, the relevance of the differential DNA methylation changes with hyperglycemia in...
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| description | Differential DNA methylation with hyperglycemia is significantly associated with Type 2 Diabetes (T2D). Longtime extended exposure to high blood glucose levels can affect the epigenetic signatures in all organs. However, the relevance of the differential DNA methylation changes with hyperglycemia in blood with pancreatic islets remains unclear. We investigated differential DNA methylation in relation to glucose homeostasis based on the Oral Glucose Tolerance Test (OGTT) in a population-based cohort. We found a total of 382 differential methylation sites from blood DNA in hyperglycemia and type 2 diabetes subgroups using a longitudinal and cross-sectional approach. Among them, three CpG sites were overlapped; they were mapped to the MSI2 and CXXC4 genes. In a DNA methylation replication study done by pyrosequencing (n = 440), the CpG site of MSI2 were shown to have strong associations with the T2D group (p value = 2.20E-16). The differential methylation of MSI2 at chr17:55484635 was associated with diabetes-related traits, in particular with insulin sensitivity (QUICKI, p value = 2.20E-16) and resistance (HOMA-IR, p value = 1.177E-07). In human pancreatic islets, at the single-base resolution (using whole-genome bisulfite sequencing), the 292 CpG sites in the ±5kb at chr17:55484635 were found to be significantly hypo-methylated in donors with T2D (average decrease = 13.91%, 95% confidence interval (CI) = 4.18~ 17.06) as compared to controls, and methylation patterns differed by sex (-9.57%, CI = -16.76~ -6.89) and age (0.12%, CI = -11.17~ 3.77). Differential methylation of the MSI2 gene (chr17:55484635) in blood and islet cells is strongly related to hyperglycemia. Our findings suggest that epigenetic perturbation on the target site of MSI2 gene in circulating blood and pancreatic islets should represent or affect hyperglycemia. |
| doi_str_mv | 10.1371/journal.pone.0177406 |
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Longtime extended exposure to high blood glucose levels can affect the epigenetic signatures in all organs. However, the relevance of the differential DNA methylation changes with hyperglycemia in blood with pancreatic islets remains unclear. We investigated differential DNA methylation in relation to glucose homeostasis based on the Oral Glucose Tolerance Test (OGTT) in a population-based cohort. We found a total of 382 differential methylation sites from blood DNA in hyperglycemia and type 2 diabetes subgroups using a longitudinal and cross-sectional approach. Among them, three CpG sites were overlapped; they were mapped to the MSI2 and CXXC4 genes. In a DNA methylation replication study done by pyrosequencing (n = 440), the CpG site of MSI2 were shown to have strong associations with the T2D group (p value = 2.20E-16). The differential methylation of MSI2 at chr17:55484635 was associated with diabetes-related traits, in particular with insulin sensitivity (QUICKI, p value = 2.20E-16) and resistance (HOMA-IR, p value = 1.177E-07). In human pancreatic islets, at the single-base resolution (using whole-genome bisulfite sequencing), the 292 CpG sites in the ±5kb at chr17:55484635 were found to be significantly hypo-methylated in donors with T2D (average decrease = 13.91%, 95% confidence interval (CI) = 4.18~ 17.06) as compared to controls, and methylation patterns differed by sex (-9.57%, CI = -16.76~ -6.89) and age (0.12%, CI = -11.17~ 3.77). Differential methylation of the MSI2 gene (chr17:55484635) in blood and islet cells is strongly related to hyperglycemia. Our findings suggest that epigenetic perturbation on the target site of MSI2 gene in circulating blood and pancreatic islets should represent or affect hyperglycemia.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0177406</identifier><identifier>PMID: 28542303</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adipose tissue ; Adult ; Aged ; Alcoholic beverages ; Alignment ; Apoptosis ; Assaying ; Biochemistry ; Bioinformatics ; Biology and life sciences ; Biomedical materials ; Bisulfite ; Blood ; Blood cells ; Body mass ; Body mass index ; Cancer ; Case-Control Studies ; CD4 antigen ; Cell death ; Computer programs ; Correlation ; CpG Islands ; Cross-Sectional Studies ; Deoxyribonucleic acid ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - metabolism ; Diabetics ; Diagnosis ; Diet ; DNA ; DNA Methylation ; Drugs ; Epidemiology ; Epigenesis, Genetic ; Epigenetics ; Fasting ; Female ; Females ; Food intake ; Gene expression ; Genetic testing ; Genetics ; Genomes ; Glucose ; Glucose Tolerance Test ; Health aspects ; Health care ; Heart ; Homeostasis ; Hormones ; Human behavior ; Humans ; Hyperglycemia ; Hyperglycemia - blood ; Hyperglycemia - genetics ; Hypoxia ; Ingestion ; Insulin ; Insulin resistance ; Islet cells ; Islets of Langerhans - metabolism ; Leukemia ; Leukocytes ; Longitudinal Studies ; Lungs ; Male ; Males ; Medicine and Health Sciences ; Methylation ; Middle Aged ; Nucleotide sequence ; Obesity ; Prospective Studies ; Replication ; Ribonucleic acid ; RNA ; RNA-Binding Proteins - genetics ; Rodents ; Science ; Stem cells ; Tobacco smoking ; Transplantation ; Transplants & implants</subject><ispartof>PloS one, 2017-05, Vol.12 (5), p.e0177406-e0177406</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Jeon 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 Jeon et al 2017 Jeon et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-6aeb19ae42b785d7bc915530d0813218570dacf5384663a53b702f97152ae4f73</citedby><cites>FETCH-LOGICAL-c692t-6aeb19ae42b785d7bc915530d0813218570dacf5384663a53b702f97152ae4f73</cites><orcidid>0000-0002-8787-8486</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/PMC5443489/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443489/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28542303$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jeon, Jae-Pil</creatorcontrib><creatorcontrib>Koh, In-Uk</creatorcontrib><creatorcontrib>Choi, Nak-Hyun</creatorcontrib><creatorcontrib>Kim, Bong-Jo</creatorcontrib><creatorcontrib>Han, Bok-Ghee</creatorcontrib><creatorcontrib>Lee, Suman</creatorcontrib><title>Differential DNA methylation of MSI2 and its correlation with diabetic traits</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Differential DNA methylation with hyperglycemia is significantly associated with Type 2 Diabetes (T2D). Longtime extended exposure to high blood glucose levels can affect the epigenetic signatures in all organs. However, the relevance of the differential DNA methylation changes with hyperglycemia in blood with pancreatic islets remains unclear. We investigated differential DNA methylation in relation to glucose homeostasis based on the Oral Glucose Tolerance Test (OGTT) in a population-based cohort. We found a total of 382 differential methylation sites from blood DNA in hyperglycemia and type 2 diabetes subgroups using a longitudinal and cross-sectional approach. Among them, three CpG sites were overlapped; they were mapped to the MSI2 and CXXC4 genes. In a DNA methylation replication study done by pyrosequencing (n = 440), the CpG site of MSI2 were shown to have strong associations with the T2D group (p value = 2.20E-16). The differential methylation of MSI2 at chr17:55484635 was associated with diabetes-related traits, in particular with insulin sensitivity (QUICKI, p value = 2.20E-16) and resistance (HOMA-IR, p value = 1.177E-07). In human pancreatic islets, at the single-base resolution (using whole-genome bisulfite sequencing), the 292 CpG sites in the ±5kb at chr17:55484635 were found to be significantly hypo-methylated in donors with T2D (average decrease = 13.91%, 95% confidence interval (CI) = 4.18~ 17.06) as compared to controls, and methylation patterns differed by sex (-9.57%, CI = -16.76~ -6.89) and age (0.12%, CI = -11.17~ 3.77). Differential methylation of the MSI2 gene (chr17:55484635) in blood and islet cells is strongly related to hyperglycemia. Our findings suggest that epigenetic perturbation on the target site of MSI2 gene in circulating blood and pancreatic islets should represent or affect hyperglycemia.</description><subject>Adipose tissue</subject><subject>Adult</subject><subject>Aged</subject><subject>Alcoholic beverages</subject><subject>Alignment</subject><subject>Apoptosis</subject><subject>Assaying</subject><subject>Biochemistry</subject><subject>Bioinformatics</subject><subject>Biology and life sciences</subject><subject>Biomedical materials</subject><subject>Bisulfite</subject><subject>Blood</subject><subject>Blood cells</subject><subject>Body mass</subject><subject>Body mass index</subject><subject>Cancer</subject><subject>Case-Control Studies</subject><subject>CD4 antigen</subject><subject>Cell death</subject><subject>Computer programs</subject><subject>Correlation</subject><subject>CpG Islands</subject><subject>Cross-Sectional Studies</subject><subject>Deoxyribonucleic acid</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diabetics</subject><subject>Diagnosis</subject><subject>Diet</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Drugs</subject><subject>Epidemiology</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>Fasting</subject><subject>Female</subject><subject>Females</subject><subject>Food intake</subject><subject>Gene expression</subject><subject>Genetic testing</subject><subject>Genetics</subject><subject>Genomes</subject><subject>Glucose</subject><subject>Glucose Tolerance Test</subject><subject>Health aspects</subject><subject>Health care</subject><subject>Heart</subject><subject>Homeostasis</subject><subject>Hormones</subject><subject>Human behavior</subject><subject>Humans</subject><subject>Hyperglycemia</subject><subject>Hyperglycemia - blood</subject><subject>Hyperglycemia - genetics</subject><subject>Hypoxia</subject><subject>Ingestion</subject><subject>Insulin</subject><subject>Insulin resistance</subject><subject>Islet cells</subject><subject>Islets of Langerhans - metabolism</subject><subject>Leukemia</subject><subject>Leukocytes</subject><subject>Longitudinal Studies</subject><subject>Lungs</subject><subject>Male</subject><subject>Males</subject><subject>Medicine and Health Sciences</subject><subject>Methylation</subject><subject>Middle Aged</subject><subject>Nucleotide sequence</subject><subject>Obesity</subject><subject>Prospective Studies</subject><subject>Replication</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA-Binding Proteins - genetics</subject><subject>Rodents</subject><subject>Science</subject><subject>Stem cells</subject><subject>Tobacco smoking</subject><subject>Transplantation</subject><subject>Transplants & implants</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>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkltv0zAYhiMEYmPwDxBEQkJw0eJz4hukauNQaWMSA24tx4fWVRoX2wH273HWbGrQLpAvbNnP-_rz57conkMwh7iC7za-D51s5zvfmTmAVUUAe1AcQ47RjCGAHx6sj4onMW4AoLhm7HFxhGpKEAb4uLg4c9aaYLrkZFuefVmUW5PW161Mznelt-XF1RKVstOlS7FUPgQznv12aV1qJxuTnCpTkBl4Wjyyso3m2TifFN8_fvh2-nl2fvlpebo4nynGUZoxaRrIpSGoqWqqq0ZxSCkGGtQQI1jTCmipbK6WMIYlxU0FkOUVpCiLbIVPipd7313roxg7EQXkAAHOKAeZWO4J7eVG7ILbynAtvHTiZsOHlZAhF94aQTHFkjCoFW8IsJY3qDbYKqs01Uyb7PV-vK1vtkar3Kwg24np9KRza7HyvwQlBJOaZ4M3o0HwP3sTk9i6qEzbys74_qZuDFlN0YC--ge9_3UjtZL5Aa6zPt-rBlOxIBwxTggdvOb3UHlos3Uqx8a6vD8RvJ0IMpPMn7SSfYxiefX1_9nLH1P29QG7NrJN6-jbfshRnIJkD6rgYwzG3jUZAjGk_rYbYki9GFOfZS8OP-hOdBtz_Be1UvtW</recordid><startdate>20170524</startdate><enddate>20170524</enddate><creator>Jeon, Jae-Pil</creator><creator>Koh, In-Uk</creator><creator>Choi, Nak-Hyun</creator><creator>Kim, Bong-Jo</creator><creator>Han, Bok-Ghee</creator><creator>Lee, Suman</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>AEUYN</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/0000-0002-8787-8486</orcidid></search><sort><creationdate>20170524</creationdate><title>Differential DNA methylation of MSI2 and its correlation with diabetic traits</title><author>Jeon, Jae-Pil ; Koh, In-Uk ; Choi, Nak-Hyun ; Kim, Bong-Jo ; Han, Bok-Ghee ; Lee, Suman</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-6aeb19ae42b785d7bc915530d0813218570dacf5384663a53b702f97152ae4f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adipose tissue</topic><topic>Adult</topic><topic>Aged</topic><topic>Alcoholic beverages</topic><topic>Alignment</topic><topic>Apoptosis</topic><topic>Assaying</topic><topic>Biochemistry</topic><topic>Bioinformatics</topic><topic>Biology and life sciences</topic><topic>Biomedical materials</topic><topic>Bisulfite</topic><topic>Blood</topic><topic>Blood cells</topic><topic>Body mass</topic><topic>Body mass index</topic><topic>Cancer</topic><topic>Case-Control Studies</topic><topic>CD4 antigen</topic><topic>Cell death</topic><topic>Computer programs</topic><topic>Correlation</topic><topic>CpG Islands</topic><topic>Cross-Sectional Studies</topic><topic>Deoxyribonucleic acid</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diabetics</topic><topic>Diagnosis</topic><topic>Diet</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Drugs</topic><topic>Epidemiology</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>Fasting</topic><topic>Female</topic><topic>Females</topic><topic>Food intake</topic><topic>Gene expression</topic><topic>Genetic testing</topic><topic>Genetics</topic><topic>Genomes</topic><topic>Glucose</topic><topic>Glucose Tolerance Test</topic><topic>Health aspects</topic><topic>Health care</topic><topic>Heart</topic><topic>Homeostasis</topic><topic>Hormones</topic><topic>Human behavior</topic><topic>Humans</topic><topic>Hyperglycemia</topic><topic>Hyperglycemia - blood</topic><topic>Hyperglycemia - genetics</topic><topic>Hypoxia</topic><topic>Ingestion</topic><topic>Insulin</topic><topic>Insulin resistance</topic><topic>Islet cells</topic><topic>Islets of Langerhans - 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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>Jeon, Jae-Pil</au><au>Koh, In-Uk</au><au>Choi, Nak-Hyun</au><au>Kim, Bong-Jo</au><au>Han, Bok-Ghee</au><au>Lee, Suman</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential DNA methylation of MSI2 and its correlation with diabetic traits</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-05-24</date><risdate>2017</risdate><volume>12</volume><issue>5</issue><spage>e0177406</spage><epage>e0177406</epage><pages>e0177406-e0177406</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Differential DNA methylation with hyperglycemia is significantly associated with Type 2 Diabetes (T2D). Longtime extended exposure to high blood glucose levels can affect the epigenetic signatures in all organs. However, the relevance of the differential DNA methylation changes with hyperglycemia in blood with pancreatic islets remains unclear. We investigated differential DNA methylation in relation to glucose homeostasis based on the Oral Glucose Tolerance Test (OGTT) in a population-based cohort. We found a total of 382 differential methylation sites from blood DNA in hyperglycemia and type 2 diabetes subgroups using a longitudinal and cross-sectional approach. Among them, three CpG sites were overlapped; they were mapped to the MSI2 and CXXC4 genes. In a DNA methylation replication study done by pyrosequencing (n = 440), the CpG site of MSI2 were shown to have strong associations with the T2D group (p value = 2.20E-16). The differential methylation of MSI2 at chr17:55484635 was associated with diabetes-related traits, in particular with insulin sensitivity (QUICKI, p value = 2.20E-16) and resistance (HOMA-IR, p value = 1.177E-07). In human pancreatic islets, at the single-base resolution (using whole-genome bisulfite sequencing), the 292 CpG sites in the ±5kb at chr17:55484635 were found to be significantly hypo-methylated in donors with T2D (average decrease = 13.91%, 95% confidence interval (CI) = 4.18~ 17.06) as compared to controls, and methylation patterns differed by sex (-9.57%, CI = -16.76~ -6.89) and age (0.12%, CI = -11.17~ 3.77). Differential methylation of the MSI2 gene (chr17:55484635) in blood and islet cells is strongly related to hyperglycemia. Our findings suggest that epigenetic perturbation on the target site of MSI2 gene in circulating blood and pancreatic islets should represent or affect hyperglycemia.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28542303</pmid><doi>10.1371/journal.pone.0177406</doi><tpages>e0177406</tpages><orcidid>https://orcid.org/0000-0002-8787-8486</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-05, Vol.12 (5), p.e0177406-e0177406 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1902096590 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adipose tissue Adult Aged Alcoholic beverages Alignment Apoptosis Assaying Biochemistry Bioinformatics Biology and life sciences Biomedical materials Bisulfite Blood Blood cells Body mass Body mass index Cancer Case-Control Studies CD4 antigen Cell death Computer programs Correlation CpG Islands Cross-Sectional Studies Deoxyribonucleic acid Diabetes Diabetes mellitus Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - genetics Diabetes Mellitus, Type 2 - metabolism Diabetics Diagnosis Diet DNA DNA Methylation Drugs Epidemiology Epigenesis, Genetic Epigenetics Fasting Female Females Food intake Gene expression Genetic testing Genetics Genomes Glucose Glucose Tolerance Test Health aspects Health care Heart Homeostasis Hormones Human behavior Humans Hyperglycemia Hyperglycemia - blood Hyperglycemia - genetics Hypoxia Ingestion Insulin Insulin resistance Islet cells Islets of Langerhans - metabolism Leukemia Leukocytes Longitudinal Studies Lungs Male Males Medicine and Health Sciences Methylation Middle Aged Nucleotide sequence Obesity Prospective Studies Replication Ribonucleic acid RNA RNA-Binding Proteins - genetics Rodents Science Stem cells Tobacco smoking Transplantation Transplants & implants |
| title | Differential DNA methylation of MSI2 and its correlation with diabetic traits |
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