Plasma Metabolite Signatures in Male Carriers of Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease
Both genetic and non-genetic factors are important in the pathophysiology of non-alcoholic fatty liver disease (NAFLD). The aim of our study was to identify novel metabolites and pathways associated with NAFLD by including both genetic and non-genetic factors in statistical analyses. We genotyped si...
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MDPI AG
2023-02-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/13/2/267 |
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| author | Lilian Fernandes Silva Jagadish Vangipurapu Anniina Oravilahti Ville Männistö Markku Laakso |
| author_facet | Lilian Fernandes Silva Jagadish Vangipurapu Anniina Oravilahti Ville Männistö Markku Laakso |
| author_sort | Lilian Fernandes Silva |
| collection | DOAJ |
| description | Both genetic and non-genetic factors are important in the pathophysiology of non-alcoholic fatty liver disease (NAFLD). The aim of our study was to identify novel metabolites and pathways associated with NAFLD by including both genetic and non-genetic factors in statistical analyses. We genotyped six genetic variants in the <i>PNPLA3, TM6SF2, MBOAT7, GCKR</i>, <i>PPP1R3B</i>, and <i>HSD17B13</i> genes reported to be associated with NAFLD. Non-targeted metabolomic profiling was performed from plasma samples. We applied a previously validated fatty liver index to identify participants with NAFLD. First, we associated the six genetic variants with 1098 metabolites in 2 339 men without NAFLD to determine the effects of the genetic variants on metabolites, and then in 2 535 men with NAFLD to determine the joint effects of genetic variants and non-genetic factors on metabolites. We identified several novel metabolites and metabolic pathways, especially for <i>PNPLA3, GCKR,</i> and <i>PPP1R38</i> variants relevant to the pathophysiology of NAFLD. Importantly, we showed that each genetic variant for NAFLD had a specific metabolite signature. The plasma metabolite signature was unique for each genetic variant, suggesting that several metabolites and different pathways are involved in the risk of NAFLD. The FLI index reliably identifies metabolites for NAFLD in large population-based studies. |
| first_indexed | 2024-03-11T08:26:15Z |
| format | Article |
| id | doaj.art-6c29663d64fd4b85a8d17ad67a974c94 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-11T08:26:15Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-6c29663d64fd4b85a8d17ad67a974c942023-11-16T22:05:13ZengMDPI AGMetabolites2218-19892023-02-0113226710.3390/metabo13020267Plasma Metabolite Signatures in Male Carriers of Genetic Variants Associated with Non-Alcoholic Fatty Liver DiseaseLilian Fernandes Silva0Jagadish Vangipurapu1Anniina Oravilahti2Ville Männistö3Markku Laakso4Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, FinlandInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, FinlandInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, FinlandInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, FinlandInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, FinlandBoth genetic and non-genetic factors are important in the pathophysiology of non-alcoholic fatty liver disease (NAFLD). The aim of our study was to identify novel metabolites and pathways associated with NAFLD by including both genetic and non-genetic factors in statistical analyses. We genotyped six genetic variants in the <i>PNPLA3, TM6SF2, MBOAT7, GCKR</i>, <i>PPP1R3B</i>, and <i>HSD17B13</i> genes reported to be associated with NAFLD. Non-targeted metabolomic profiling was performed from plasma samples. We applied a previously validated fatty liver index to identify participants with NAFLD. First, we associated the six genetic variants with 1098 metabolites in 2 339 men without NAFLD to determine the effects of the genetic variants on metabolites, and then in 2 535 men with NAFLD to determine the joint effects of genetic variants and non-genetic factors on metabolites. We identified several novel metabolites and metabolic pathways, especially for <i>PNPLA3, GCKR,</i> and <i>PPP1R38</i> variants relevant to the pathophysiology of NAFLD. Importantly, we showed that each genetic variant for NAFLD had a specific metabolite signature. The plasma metabolite signature was unique for each genetic variant, suggesting that several metabolites and different pathways are involved in the risk of NAFLD. The FLI index reliably identifies metabolites for NAFLD in large population-based studies.https://www.mdpi.com/2218-1989/13/2/267non-alcoholic fatty liver diseasegenetic variantsmetabolomics |
| spellingShingle | Lilian Fernandes Silva Jagadish Vangipurapu Anniina Oravilahti Ville Männistö Markku Laakso Plasma Metabolite Signatures in Male Carriers of Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease Metabolites non-alcoholic fatty liver disease genetic variants metabolomics |
| title | Plasma Metabolite Signatures in Male Carriers of Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease |
| title_full | Plasma Metabolite Signatures in Male Carriers of Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease |
| title_fullStr | Plasma Metabolite Signatures in Male Carriers of Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease |
| title_full_unstemmed | Plasma Metabolite Signatures in Male Carriers of Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease |
| title_short | Plasma Metabolite Signatures in Male Carriers of Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease |
| title_sort | plasma metabolite signatures in male carriers of genetic variants associated with non alcoholic fatty liver disease |
| topic | non-alcoholic fatty liver disease genetic variants metabolomics |
| url | https://www.mdpi.com/2218-1989/13/2/267 |
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