Genetic Variants Associated with Elevated Plasma Ceramides in Individuals with Metabolic Syndrome
Metabolic syndrome (MetS) is a complex condition of metabolic disorders and shows a steady onset globally. Ceramides are known as intracellular signaling molecules that influence key metabolism through various pathways such as MetS and insulin resistance. Therefore, it is important to identify novel...
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| Veröffentlicht in: | Genes 2022-08, Vol.13 (8), p.1497 |
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| creator | Lee, Sanghoo Kim, Seol-A Kim, Yejin Kim, Juhoon Hong, Gayeon Hong, Jeonghoon Choi, Kyeonghwan Eom, Chun-Sick Baik, Saeyun Lee, Mi-Kyeong Lee, Kyoung-Ryul |
| description | Metabolic syndrome (MetS) is a complex condition of metabolic disorders and shows a steady onset globally. Ceramides are known as intracellular signaling molecules that influence key metabolism through various pathways such as MetS and insulin resistance. Therefore, it is important to identify novel genetic factors related to increased plasma ceramides in subjects with MetS. Here we first measured plasma ceramides levels in 37 subjects with MetS and in 38 healthy subjects by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Specifically, levels of C16 ceramide (Cer-16), C18 ceramide (Cer-18), C20 ceramide (Cer-20), C18 dihydroceramide (DhCer-18), C24 dihydroceramide (DhCer-24), and C24:1 dihydroceramide (DhCer-24:1) were significantly increased in MetS group (p < 5.0 × 10−2). We then performed single nucleotide polymorphism (SNP) genotyping to identify variants associated with elevated plasma ceramides in MetS group using Axiom® Korea Biobank Array v1.1 chip. We also performed linear regression analysis on genetic variants involved in ceramide synthesis and significantly elevated plasma ceramides and dihydroceramides. Ten variants (rs75397325, rs4246316, rs80165332, rs62106618, rs12358192, rs11006229, rs10826014, rs149162405, rs6109681, and rs3906631) across six genes (ACER1, CERS3, CERS6, SGMS1, SPTLC2, and SPTLC3) functionally involved in ceramide biosynthesis showed significant associations with the elevated levels of at least one of the ceramide species in MetS group at a statistically significant threshold of false discovery rate (FDR)-adjusted p < 5.0 × 10−2. Our findings suggest that the variants may be genetic determinants associated with increased plasma ceramides in individuals with MetS. |
| doi_str_mv | 10.3390/genes13081497 |
| format | Article |
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Ceramides are known as intracellular signaling molecules that influence key metabolism through various pathways such as MetS and insulin resistance. Therefore, it is important to identify novel genetic factors related to increased plasma ceramides in subjects with MetS. Here we first measured plasma ceramides levels in 37 subjects with MetS and in 38 healthy subjects by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Specifically, levels of C16 ceramide (Cer-16), C18 ceramide (Cer-18), C20 ceramide (Cer-20), C18 dihydroceramide (DhCer-18), C24 dihydroceramide (DhCer-24), and C24:1 dihydroceramide (DhCer-24:1) were significantly increased in MetS group (p < 5.0 × 10−2). We then performed single nucleotide polymorphism (SNP) genotyping to identify variants associated with elevated plasma ceramides in MetS group using Axiom® Korea Biobank Array v1.1 chip. We also performed linear regression analysis on genetic variants involved in ceramide synthesis and significantly elevated plasma ceramides and dihydroceramides. Ten variants (rs75397325, rs4246316, rs80165332, rs62106618, rs12358192, rs11006229, rs10826014, rs149162405, rs6109681, and rs3906631) across six genes (ACER1, CERS3, CERS6, SGMS1, SPTLC2, and SPTLC3) functionally involved in ceramide biosynthesis showed significant associations with the elevated levels of at least one of the ceramide species in MetS group at a statistically significant threshold of false discovery rate (FDR)-adjusted p < 5.0 × 10−2. Our findings suggest that the variants may be genetic determinants associated with increased plasma ceramides in individuals with MetS.</description><identifier>ISSN: 2073-4425</identifier><identifier>EISSN: 2073-4425</identifier><identifier>DOI: 10.3390/genes13081497</identifier><identifier>PMID: 36011408</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Biobanks ; Blood plasma ; Ceramide ; Ceramides ; Ceramides - genetics ; Chromatography, Liquid ; Communication ; Diabetes ; Genetic analysis ; Genetic aspects ; Genetic diversity ; Genetic factors ; Genetic testing ; Genomes ; Genotyping ; Humans ; Hypertension ; Insulin ; Insulin Resistance ; Intracellular signalling ; Lipids ; Liquid chromatography ; Mass spectrometry ; Mass spectroscopy ; Metabolic diseases ; Metabolic disorders ; Metabolic syndrome ; Metabolic Syndrome - genetics ; Methods ; Obesity ; Physiological aspects ; Plasma ; Signal transduction ; Single-nucleotide polymorphism ; Solvents ; Statistical analysis ; Tandem Mass Spectrometry</subject><ispartof>Genes, 2022-08, Vol.13 (8), p.1497</ispartof><rights>COPYRIGHT 2022 MDPI AG</rights><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c482t-bc515ad61f5b97452530fca0c90c50e1452a0e352765f43571e94c2693d837b63</citedby><cites>FETCH-LOGICAL-c482t-bc515ad61f5b97452530fca0c90c50e1452a0e352765f43571e94c2693d837b63</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/PMC9407997/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9407997/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36011408$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Sanghoo</creatorcontrib><creatorcontrib>Kim, Seol-A</creatorcontrib><creatorcontrib>Kim, Yejin</creatorcontrib><creatorcontrib>Kim, Juhoon</creatorcontrib><creatorcontrib>Hong, Gayeon</creatorcontrib><creatorcontrib>Hong, Jeonghoon</creatorcontrib><creatorcontrib>Choi, Kyeonghwan</creatorcontrib><creatorcontrib>Eom, Chun-Sick</creatorcontrib><creatorcontrib>Baik, Saeyun</creatorcontrib><creatorcontrib>Lee, Mi-Kyeong</creatorcontrib><creatorcontrib>Lee, Kyoung-Ryul</creatorcontrib><title>Genetic Variants Associated with Elevated Plasma Ceramides in Individuals with Metabolic Syndrome</title><title>Genes</title><addtitle>Genes (Basel)</addtitle><description>Metabolic syndrome (MetS) is a complex condition of metabolic disorders and shows a steady onset globally. Ceramides are known as intracellular signaling molecules that influence key metabolism through various pathways such as MetS and insulin resistance. Therefore, it is important to identify novel genetic factors related to increased plasma ceramides in subjects with MetS. Here we first measured plasma ceramides levels in 37 subjects with MetS and in 38 healthy subjects by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Specifically, levels of C16 ceramide (Cer-16), C18 ceramide (Cer-18), C20 ceramide (Cer-20), C18 dihydroceramide (DhCer-18), C24 dihydroceramide (DhCer-24), and C24:1 dihydroceramide (DhCer-24:1) were significantly increased in MetS group (p < 5.0 × 10−2). We then performed single nucleotide polymorphism (SNP) genotyping to identify variants associated with elevated plasma ceramides in MetS group using Axiom® Korea Biobank Array v1.1 chip. We also performed linear regression analysis on genetic variants involved in ceramide synthesis and significantly elevated plasma ceramides and dihydroceramides. Ten variants (rs75397325, rs4246316, rs80165332, rs62106618, rs12358192, rs11006229, rs10826014, rs149162405, rs6109681, and rs3906631) across six genes (ACER1, CERS3, CERS6, SGMS1, SPTLC2, and SPTLC3) functionally involved in ceramide biosynthesis showed significant associations with the elevated levels of at least one of the ceramide species in MetS group at a statistically significant threshold of false discovery rate (FDR)-adjusted p < 5.0 × 10−2. Our findings suggest that the variants may be genetic determinants associated with increased plasma ceramides in individuals with MetS.</description><subject>Biobanks</subject><subject>Blood plasma</subject><subject>Ceramide</subject><subject>Ceramides</subject><subject>Ceramides - genetics</subject><subject>Chromatography, Liquid</subject><subject>Communication</subject><subject>Diabetes</subject><subject>Genetic analysis</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic factors</subject><subject>Genetic testing</subject><subject>Genomes</subject><subject>Genotyping</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Insulin</subject><subject>Insulin Resistance</subject><subject>Intracellular signalling</subject><subject>Lipids</subject><subject>Liquid chromatography</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Metabolic diseases</subject><subject>Metabolic disorders</subject><subject>Metabolic syndrome</subject><subject>Metabolic Syndrome - genetics</subject><subject>Methods</subject><subject>Obesity</subject><subject>Physiological aspects</subject><subject>Plasma</subject><subject>Signal transduction</subject><subject>Single-nucleotide polymorphism</subject><subject>Solvents</subject><subject>Statistical analysis</subject><subject>Tandem Mass Spectrometry</subject><issn>2073-4425</issn><issn>2073-4425</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkk1P3DAQhqOqqCDKsdcqUi-9BMZfcXyptFpRQAIVqR9Xy3Emi1FiUztZxL-vlwXKVrUPHs8881pjvUXxgcAxYwpOVugxEQYN4Uq-KQ4oSFZxTsXbV_F-cZTSLeTFgQKId8U-q4EQDs1BYc6yxORs-ctEZ_yUykVKwTozYVfeu-mmPB1w_Xi7HkwaTbnEaEbXYSqdLy9859aum82QtvQVTqYNQxb8_uC7GEZ8X-z1uYxHT-dh8fPr6Y_leXX57exiubisLG_oVLVWEGG6mvSiVZILKhj01oBVYAUgyRkDyASVteg5E5Kg4pbWinUNk23NDosvW927uR2xs-inaAZ9F91o4oMOxundinc3ehXWWnGQSsks8PlJIIbfM6ZJjy5ZHAbjMcxJUwmyBlFLntFP_6C3YY4-j7ehaqIaxpq_1MoMqJ3vQ37XbkT1QlLOJYVH6vg_VN4djs4Gj73L-Z2GattgY0gpYv8yIwG9sYXesUXmP77-mBf62QTsDzT3sd4</recordid><startdate>20220822</startdate><enddate>20220822</enddate><creator>Lee, Sanghoo</creator><creator>Kim, Seol-A</creator><creator>Kim, Yejin</creator><creator>Kim, Juhoon</creator><creator>Hong, Gayeon</creator><creator>Hong, Jeonghoon</creator><creator>Choi, Kyeonghwan</creator><creator>Eom, Chun-Sick</creator><creator>Baik, Saeyun</creator><creator>Lee, Mi-Kyeong</creator><creator>Lee, Kyoung-Ryul</creator><general>MDPI AG</general><general>MDPI</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>8FD</scope><scope>8FE</scope><scope>8FH</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>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</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>20220822</creationdate><title>Genetic Variants Associated with Elevated Plasma Ceramides in Individuals with Metabolic Syndrome</title><author>Lee, Sanghoo ; Kim, Seol-A ; Kim, Yejin ; Kim, Juhoon ; Hong, Gayeon ; Hong, Jeonghoon ; Choi, Kyeonghwan ; Eom, Chun-Sick ; Baik, Saeyun ; Lee, Mi-Kyeong ; Lee, Kyoung-Ryul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c482t-bc515ad61f5b97452530fca0c90c50e1452a0e352765f43571e94c2693d837b63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Biobanks</topic><topic>Blood plasma</topic><topic>Ceramide</topic><topic>Ceramides</topic><topic>Ceramides - genetics</topic><topic>Chromatography, Liquid</topic><topic>Communication</topic><topic>Diabetes</topic><topic>Genetic analysis</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genetic factors</topic><topic>Genetic testing</topic><topic>Genomes</topic><topic>Genotyping</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Insulin</topic><topic>Insulin Resistance</topic><topic>Intracellular signalling</topic><topic>Lipids</topic><topic>Liquid chromatography</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Metabolic diseases</topic><topic>Metabolic disorders</topic><topic>Metabolic syndrome</topic><topic>Metabolic Syndrome - genetics</topic><topic>Methods</topic><topic>Obesity</topic><topic>Physiological aspects</topic><topic>Plasma</topic><topic>Signal transduction</topic><topic>Single-nucleotide polymorphism</topic><topic>Solvents</topic><topic>Statistical analysis</topic><topic>Tandem Mass Spectrometry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Sanghoo</creatorcontrib><creatorcontrib>Kim, Seol-A</creatorcontrib><creatorcontrib>Kim, Yejin</creatorcontrib><creatorcontrib>Kim, Juhoon</creatorcontrib><creatorcontrib>Hong, Gayeon</creatorcontrib><creatorcontrib>Hong, Jeonghoon</creatorcontrib><creatorcontrib>Choi, Kyeonghwan</creatorcontrib><creatorcontrib>Eom, Chun-Sick</creatorcontrib><creatorcontrib>Baik, Saeyun</creatorcontrib><creatorcontrib>Lee, Mi-Kyeong</creatorcontrib><creatorcontrib>Lee, Kyoung-Ryul</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</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>Genes</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Sanghoo</au><au>Kim, Seol-A</au><au>Kim, Yejin</au><au>Kim, Juhoon</au><au>Hong, Gayeon</au><au>Hong, Jeonghoon</au><au>Choi, Kyeonghwan</au><au>Eom, Chun-Sick</au><au>Baik, Saeyun</au><au>Lee, Mi-Kyeong</au><au>Lee, Kyoung-Ryul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Variants Associated with Elevated Plasma Ceramides in Individuals with Metabolic Syndrome</atitle><jtitle>Genes</jtitle><addtitle>Genes (Basel)</addtitle><date>2022-08-22</date><risdate>2022</risdate><volume>13</volume><issue>8</issue><spage>1497</spage><pages>1497-</pages><issn>2073-4425</issn><eissn>2073-4425</eissn><abstract>Metabolic syndrome (MetS) is a complex condition of metabolic disorders and shows a steady onset globally. Ceramides are known as intracellular signaling molecules that influence key metabolism through various pathways such as MetS and insulin resistance. Therefore, it is important to identify novel genetic factors related to increased plasma ceramides in subjects with MetS. Here we first measured plasma ceramides levels in 37 subjects with MetS and in 38 healthy subjects by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Specifically, levels of C16 ceramide (Cer-16), C18 ceramide (Cer-18), C20 ceramide (Cer-20), C18 dihydroceramide (DhCer-18), C24 dihydroceramide (DhCer-24), and C24:1 dihydroceramide (DhCer-24:1) were significantly increased in MetS group (p < 5.0 × 10−2). We then performed single nucleotide polymorphism (SNP) genotyping to identify variants associated with elevated plasma ceramides in MetS group using Axiom® Korea Biobank Array v1.1 chip. We also performed linear regression analysis on genetic variants involved in ceramide synthesis and significantly elevated plasma ceramides and dihydroceramides. Ten variants (rs75397325, rs4246316, rs80165332, rs62106618, rs12358192, rs11006229, rs10826014, rs149162405, rs6109681, and rs3906631) across six genes (ACER1, CERS3, CERS6, SGMS1, SPTLC2, and SPTLC3) functionally involved in ceramide biosynthesis showed significant associations with the elevated levels of at least one of the ceramide species in MetS group at a statistically significant threshold of false discovery rate (FDR)-adjusted p < 5.0 × 10−2. Our findings suggest that the variants may be genetic determinants associated with increased plasma ceramides in individuals with MetS.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36011408</pmid><doi>10.3390/genes13081497</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Biobanks Blood plasma Ceramide Ceramides Ceramides - genetics Chromatography, Liquid Communication Diabetes Genetic analysis Genetic aspects Genetic diversity Genetic factors Genetic testing Genomes Genotyping Humans Hypertension Insulin Insulin Resistance Intracellular signalling Lipids Liquid chromatography Mass spectrometry Mass spectroscopy Metabolic diseases Metabolic disorders Metabolic syndrome Metabolic Syndrome - genetics Methods Obesity Physiological aspects Plasma Signal transduction Single-nucleotide polymorphism Solvents Statistical analysis Tandem Mass Spectrometry |
| title | Genetic Variants Associated with Elevated Plasma Ceramides in Individuals with Metabolic Syndrome |
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