The Genetic Variability of Members of the SLC38 Family of Amino Acid Transporters (<i>SLC38A3</i>, <i>SLC38A7</i> and <i>SLC38A9</i>) Affects Susceptibility to Type 2 Diabetes and Vascular Complications
Type 2 Diabetes (T2D) is a metabolic disease associated with long-term complications, with a multifactorial pathogenesis related to the interplay between genetic and modifiable risk factors, of which nutrition is the most relevant. In particular, the importance of proteins and constitutive amino aci...
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MDPI AG
2022-10-01
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| Online Access: | https://www.mdpi.com/2072-6643/14/21/4440 |
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| author | Paolina Crocco Serena Dato Alberto Montesanto Anna Rita Bonfigli Roberto Testa Fabiola Olivieri Giuseppe Passarino Giuseppina Rose |
| author_facet | Paolina Crocco Serena Dato Alberto Montesanto Anna Rita Bonfigli Roberto Testa Fabiola Olivieri Giuseppe Passarino Giuseppina Rose |
| author_sort | Paolina Crocco |
| collection | DOAJ |
| description | Type 2 Diabetes (T2D) is a metabolic disease associated with long-term complications, with a multifactorial pathogenesis related to the interplay between genetic and modifiable risk factors, of which nutrition is the most relevant. In particular, the importance of proteins and constitutive amino acids (AAs) in disease susceptibility is emerging. The ability to sense and respond to changes in AA supplies is mediated by complex networks, of which AA transporters (AATs) are crucial components acting also as sensors of AA availability. This study explored the associations between polymorphisms in selected AATs genes and T2D and vascular complications in 433 patients and 506 healthy controls. Analyses revealed significant association of <i>SLC38A3</i>-rs1858828 with disease risk. Stratification of patients based on presence/absence of vascular complications highlighted significant associations of <i>SLC7A8</i>-rs3783436 and <i>SLC38A7</i>-rs9806843 with diabetic retinopathy. Additionally, the <i>SLC38A9</i>-rs4865615 resulted associated with chronic kidney disease. Notably, these genes function as AAs sensors, specifically glutamine, leucine, and arginine, linked to the main nutrient signaling pathway mammalian target of rapamycin complex 1 (mTORC1). Thus, their genetic variability may contribute to T2D by influencing the ability to properly transduce a signal activating mTORC1 in response to AA availability. In this scenario, the contribution of dietary AAs supply to disease risk may be relevant. |
| first_indexed | 2024-03-09T18:46:38Z |
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| id | doaj.art-0b2ccbc3446d48828c7a4b8d19a36004 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T18:46:38Z |
| publishDate | 2022-10-01 |
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| series | Nutrients |
| spelling | doaj.art-0b2ccbc3446d48828c7a4b8d19a360042023-11-24T06:11:30ZengMDPI AGNutrients2072-66432022-10-011421444010.3390/nu14214440The Genetic Variability of Members of the SLC38 Family of Amino Acid Transporters (<i>SLC38A3</i>, <i>SLC38A7</i> and <i>SLC38A9</i>) Affects Susceptibility to Type 2 Diabetes and Vascular ComplicationsPaolina Crocco0Serena Dato1Alberto Montesanto2Anna Rita Bonfigli3Roberto Testa4Fabiola Olivieri5Giuseppe Passarino6Giuseppina Rose7Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, ItalyScientific Direction, IRCCS INRCA, 60121 Ancona, ItalyClinic of Laboratory and Precision Medicine, IRCCS INRCA, 60121 Ancona, ItalyClinic of Laboratory and Precision Medicine, IRCCS INRCA, 60121 Ancona, ItalyDepartment of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, ItalyType 2 Diabetes (T2D) is a metabolic disease associated with long-term complications, with a multifactorial pathogenesis related to the interplay between genetic and modifiable risk factors, of which nutrition is the most relevant. In particular, the importance of proteins and constitutive amino acids (AAs) in disease susceptibility is emerging. The ability to sense and respond to changes in AA supplies is mediated by complex networks, of which AA transporters (AATs) are crucial components acting also as sensors of AA availability. This study explored the associations between polymorphisms in selected AATs genes and T2D and vascular complications in 433 patients and 506 healthy controls. Analyses revealed significant association of <i>SLC38A3</i>-rs1858828 with disease risk. Stratification of patients based on presence/absence of vascular complications highlighted significant associations of <i>SLC7A8</i>-rs3783436 and <i>SLC38A7</i>-rs9806843 with diabetic retinopathy. Additionally, the <i>SLC38A9</i>-rs4865615 resulted associated with chronic kidney disease. Notably, these genes function as AAs sensors, specifically glutamine, leucine, and arginine, linked to the main nutrient signaling pathway mammalian target of rapamycin complex 1 (mTORC1). Thus, their genetic variability may contribute to T2D by influencing the ability to properly transduce a signal activating mTORC1 in response to AA availability. In this scenario, the contribution of dietary AAs supply to disease risk may be relevant.https://www.mdpi.com/2072-6643/14/21/4440Type 2 Diabetesdiabetes complicationsamino acid transportersSLC38 familygenetic variabilityamino acid availability |
| spellingShingle | Paolina Crocco Serena Dato Alberto Montesanto Anna Rita Bonfigli Roberto Testa Fabiola Olivieri Giuseppe Passarino Giuseppina Rose The Genetic Variability of Members of the SLC38 Family of Amino Acid Transporters (<i>SLC38A3</i>, <i>SLC38A7</i> and <i>SLC38A9</i>) Affects Susceptibility to Type 2 Diabetes and Vascular Complications Nutrients Type 2 Diabetes diabetes complications amino acid transporters SLC38 family genetic variability amino acid availability |
| title | The Genetic Variability of Members of the SLC38 Family of Amino Acid Transporters (<i>SLC38A3</i>, <i>SLC38A7</i> and <i>SLC38A9</i>) Affects Susceptibility to Type 2 Diabetes and Vascular Complications |
| title_full | The Genetic Variability of Members of the SLC38 Family of Amino Acid Transporters (<i>SLC38A3</i>, <i>SLC38A7</i> and <i>SLC38A9</i>) Affects Susceptibility to Type 2 Diabetes and Vascular Complications |
| title_fullStr | The Genetic Variability of Members of the SLC38 Family of Amino Acid Transporters (<i>SLC38A3</i>, <i>SLC38A7</i> and <i>SLC38A9</i>) Affects Susceptibility to Type 2 Diabetes and Vascular Complications |
| title_full_unstemmed | The Genetic Variability of Members of the SLC38 Family of Amino Acid Transporters (<i>SLC38A3</i>, <i>SLC38A7</i> and <i>SLC38A9</i>) Affects Susceptibility to Type 2 Diabetes and Vascular Complications |
| title_short | The Genetic Variability of Members of the SLC38 Family of Amino Acid Transporters (<i>SLC38A3</i>, <i>SLC38A7</i> and <i>SLC38A9</i>) Affects Susceptibility to Type 2 Diabetes and Vascular Complications |
| title_sort | genetic variability of members of the slc38 family of amino acid transporters i slc38a3 i i slc38a7 i and i slc38a9 i affects susceptibility to type 2 diabetes and vascular complications |
| topic | Type 2 Diabetes diabetes complications amino acid transporters SLC38 family genetic variability amino acid availability |
| url | https://www.mdpi.com/2072-6643/14/21/4440 |
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