Polymorphisms in glucose homeostasis genes are associated with cardiovascular and renal parameters in patients with diabetic nephropathy
Background Diabetic nephropathy (DN) has become the major cause of end-stage kidney disease and is associated to an extremely high cardiovascular (CV) risk.Methods We screened 318 DN patients for 23 SNPs in four glucose transporters (SLC2A1, SLC2A2, SLC5A1 and SLC5A2) and in KCNJ11 and ABCC8, which...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Annals of Medicine |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/07853890.2022.2138531 |
| _version_ | 1797991795673530368 |
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| author | Sonia Mota-Zamorano Luz M. González Nicolás R. Robles José M. Valdivielso José C. Arévalo-Lorido Juan López-Gómez Guillermo Gervasini |
| author_facet | Sonia Mota-Zamorano Luz M. González Nicolás R. Robles José M. Valdivielso José C. Arévalo-Lorido Juan López-Gómez Guillermo Gervasini |
| author_sort | Sonia Mota-Zamorano |
| collection | DOAJ |
| description | Background Diabetic nephropathy (DN) has become the major cause of end-stage kidney disease and is associated to an extremely high cardiovascular (CV) risk.Methods We screened 318 DN patients for 23 SNPs in four glucose transporters (SLC2A1, SLC2A2, SLC5A1 and SLC5A2) and in KCNJ11 and ABCC8, which participate in insulin secretion. Regression models were utilised to identify associations with renal parameters, atherosclerosis measurements and CV events. In addition, 506 individuals with normal renal function were also genotyped as a control group.Results In the patient’s cohort, common carotid intima media thickness values were higher in carriers of ABCC8 rs3758953 and rs2188966 vs. non-carriers [0.78(0.25) vs. 0.72(0.22) mm, p < 0.05 and 0.79(0.26) vs. 0.72(0.22) mm, p < 0.05], respectively. Furthermore, ABCC8 rs1799859 was linked to presence of plaque in these patients [1.89(1.03-3.46), p < 0.05]. Two variants, SLC2A2 rs8192675 and SLC5A2 rs9924771, were associated with better [OR = 0.49 (0.30-0.81), p < 0.01] and worse [OR = 1.92 (1.15-3.21), p < 0.05] CV event-free survival, respectively. With regard to renal variables, rs841848 and rs710218 in SLC2A1, as well as rs3813008 in SLC5A2, significantly altered estimated glomerular filtration rate values [carriers vs. non-carriers: 30.41(22.57) vs. 28.25(20.10), p < 0.05; 28.95(21.11) vs. 29.52(21.66), p < 0.05 and 32.03(18.06) vs. 28.14(23.06) ml/min/1.73 m2, p < 0.05]. In addition, ABCC8 rs3758947 was associated with higher albumin-to-creatinine ratios [193.5(1139.91) vs. 160(652.90) mg/g, p < 0.05]. The epistasis analysis of SNP-pairs interactions showed that ABCC8 rs3758947 interacted with several SNPs in SLC2A2 to significantly affect CV events (p < 0.01). No SNPs were associated with DN risk.Conclusions Polymorphisms in genes determining glucose homeostasis may play a relevant role in renal parameters and CV-related outcomes of DN patients. |
| first_indexed | 2024-04-11T08:57:56Z |
| format | Article |
| id | doaj.art-fc02b76432544e2ba0cf5139d46a9c47 |
| institution | Directory Open Access Journal |
| issn | 0785-3890 1365-2060 |
| language | English |
| last_indexed | 2024-04-11T08:57:56Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Annals of Medicine |
| spelling | doaj.art-fc02b76432544e2ba0cf5139d46a9c472022-12-22T04:33:10ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602022-12-015413039305110.1080/07853890.2022.2138531Polymorphisms in glucose homeostasis genes are associated with cardiovascular and renal parameters in patients with diabetic nephropathySonia Mota-Zamorano0Luz M. González1Nicolás R. Robles2José M. Valdivielso3José C. Arévalo-Lorido4Juan López-Gómez5Guillermo Gervasini6Department of Medical and Surgical Therapeutics, Medical School, Universidad de Extremadura, Badajoz, SpainDepartment of Medical and Surgical Therapeutics, Medical School, Universidad de Extremadura, Badajoz, SpainRICORS2040 Renal Research Network, Madrid, SpainRICORS2040 Renal Research Network, Madrid, SpainService of Internal Medicine, Badajoz University Hospital, Badajoz, SpainService of Clinical Analyses, Badajoz University Hospital, Badajoz, SpainDepartment of Medical and Surgical Therapeutics, Medical School, Universidad de Extremadura, Badajoz, SpainBackground Diabetic nephropathy (DN) has become the major cause of end-stage kidney disease and is associated to an extremely high cardiovascular (CV) risk.Methods We screened 318 DN patients for 23 SNPs in four glucose transporters (SLC2A1, SLC2A2, SLC5A1 and SLC5A2) and in KCNJ11 and ABCC8, which participate in insulin secretion. Regression models were utilised to identify associations with renal parameters, atherosclerosis measurements and CV events. In addition, 506 individuals with normal renal function were also genotyped as a control group.Results In the patient’s cohort, common carotid intima media thickness values were higher in carriers of ABCC8 rs3758953 and rs2188966 vs. non-carriers [0.78(0.25) vs. 0.72(0.22) mm, p < 0.05 and 0.79(0.26) vs. 0.72(0.22) mm, p < 0.05], respectively. Furthermore, ABCC8 rs1799859 was linked to presence of plaque in these patients [1.89(1.03-3.46), p < 0.05]. Two variants, SLC2A2 rs8192675 and SLC5A2 rs9924771, were associated with better [OR = 0.49 (0.30-0.81), p < 0.01] and worse [OR = 1.92 (1.15-3.21), p < 0.05] CV event-free survival, respectively. With regard to renal variables, rs841848 and rs710218 in SLC2A1, as well as rs3813008 in SLC5A2, significantly altered estimated glomerular filtration rate values [carriers vs. non-carriers: 30.41(22.57) vs. 28.25(20.10), p < 0.05; 28.95(21.11) vs. 29.52(21.66), p < 0.05 and 32.03(18.06) vs. 28.14(23.06) ml/min/1.73 m2, p < 0.05]. In addition, ABCC8 rs3758947 was associated with higher albumin-to-creatinine ratios [193.5(1139.91) vs. 160(652.90) mg/g, p < 0.05]. The epistasis analysis of SNP-pairs interactions showed that ABCC8 rs3758947 interacted with several SNPs in SLC2A2 to significantly affect CV events (p < 0.01). No SNPs were associated with DN risk.Conclusions Polymorphisms in genes determining glucose homeostasis may play a relevant role in renal parameters and CV-related outcomes of DN patients.https://www.tandfonline.com/doi/10.1080/07853890.2022.2138531Chronic kidney diseasediabetic kidney diseasediabetic nephropathytype 2 diabetes mellitusglucose homeostasis |
| spellingShingle | Sonia Mota-Zamorano Luz M. González Nicolás R. Robles José M. Valdivielso José C. Arévalo-Lorido Juan López-Gómez Guillermo Gervasini Polymorphisms in glucose homeostasis genes are associated with cardiovascular and renal parameters in patients with diabetic nephropathy Annals of Medicine Chronic kidney disease diabetic kidney disease diabetic nephropathy type 2 diabetes mellitus glucose homeostasis |
| title | Polymorphisms in glucose homeostasis genes are associated with cardiovascular and renal parameters in patients with diabetic nephropathy |
| title_full | Polymorphisms in glucose homeostasis genes are associated with cardiovascular and renal parameters in patients with diabetic nephropathy |
| title_fullStr | Polymorphisms in glucose homeostasis genes are associated with cardiovascular and renal parameters in patients with diabetic nephropathy |
| title_full_unstemmed | Polymorphisms in glucose homeostasis genes are associated with cardiovascular and renal parameters in patients with diabetic nephropathy |
| title_short | Polymorphisms in glucose homeostasis genes are associated with cardiovascular and renal parameters in patients with diabetic nephropathy |
| title_sort | polymorphisms in glucose homeostasis genes are associated with cardiovascular and renal parameters in patients with diabetic nephropathy |
| topic | Chronic kidney disease diabetic kidney disease diabetic nephropathy type 2 diabetes mellitus glucose homeostasis |
| url | https://www.tandfonline.com/doi/10.1080/07853890.2022.2138531 |
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