Plasma Thrombin-activatable Fibrinolysis Inhibitor and the 1040C/T Polymorphism Are Risk Factors for Diabetic Kidney Disease in Chinese Patients with Type 2 Diabetes

Overview

Journal PeerJ

Specialties Biology
Environmental Health
General Medicine

Date 2023 Nov 29

PMID 38025709

Authors

Qinghua Huang

Dujin Feng

Lianlian Pan

Huan Wang

Yan Wu

Bin Zhong

Jianguang Gong

Huijun Lin

Xianming Fei

Affiliations

Soon will be listed here.

Abstract

Background: Inflammatory and hemostatic disorders in diabetic microangiopathy (DMA) can be linked to thrombin-activatable fibrinolysis inhibitor (TAFI) and its own gene polymorphisms. Thus, the study aimed to investigate the associations of plasma TAFI and gene polymorphisms with DMA in Chinese patients with type 2 diabetes (T2D).

Methods: Plasma TAFI of 223 patients with T2D was measured, and the genotypes and alleles of the 1040C/T, 438G/A, and 505G/A polymorphisms of the gene were analyzed. A ROC curve was constructed to evaluate the identifying power of TAFI between patients with T2D and DMA, and logistic regression analysis was used to observe the correlation of plasma TAFI and gene polymorphisms with the risk for DMA.

Results: Plasma TAFI was higher in patients with DMA than in patients with only T2D ( < 0.05). TAFI exhibited the largest area under ROC in identifying diabetic kidney disease (DKD) from only T2D (0.763, 95% CI [0.674-0.853], < 0.01), and adjusted multivariate analysis showed a high odds ratio (OR: 15.72, 95% CI [4.573-53.987], < 0.001) for DKD. Higher frequencies of the CT genotype and T allele of the 1040C/T polymorphism were found in DKD compared with only T2D (respectively < 0.05), and the CT genotype exhibited a high OR (1.623, 95% CI [1.173-2.710], < 0.05) for DKD. DKD patients with the CT genotype had higher plasma TAFI levels, while T2D and DKD patients with CC/TT genotypes had lower plasma TAFI levels.

Conclusion: Plasma TAFI and the CT genotype and T allele of the 1040C/T polymorphism are independent risk factors for DKD in Chinese T2D patients.

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References

Zheng C, Li X, Kong C, Ke S, Peng C, Cui T . Effect of single nucleotide polymorphism in thrombin-activatable fibrinolysis inhibitor on the risk of diabetic macrovascular disease. Blood Coagul Fibrinolysis. 2014; 26(2):185-90. DOI: 10.1097/MBC.0000000000000216. View

Lyssenko V, Vaag A . Genetics of diabetes-associated microvascular complications. Diabetologia. 2023; 66(9):1601-1613. PMC: 10390394. DOI: 10.1007/s00125-023-05964-x. View

Xu C, Wu X, Ma X, Wang Y, Zhang B, Zhao J . Genetic variation in thrombin-activatable fibrinolysis inhibitor is associated with the risk of diabetic nephropathy. J Endocrinol Invest. 2012; 35(7):620-4. DOI: 10.1007/BF03345800. View

Ziegler D, Porta M, Papanas N, Mota M, Jermendy G, Beltramo E . The Role of Biofactors in Diabetic Microvascular Complications. Curr Diabetes Rev. 2021; 18(4):e250821195830. PMC: 10155884. DOI: 10.2174/1871527320666210825112240. View

Wu C, Wu D, Lin M, Zhong Y . The Associations between Paraoxonase 1 L55M/Q192R Genetic Polymorphisms and the Susceptibilities of Diabetic Macroangiopathy and Diabetic Microangiopathy: A Meta-Analysis. Diabetes Ther. 2018; 9(4):1669-1688. PMC: 6064588. DOI: 10.1007/s13300-018-0466-5. View

Camera A, Hopps E, Caimi G . Diabetic microangiopathy: physiopathological, clinical and therapeutic aspects. Minerva Endocrinol. 2007; 32(3):209-29. View

Zhang Z, Zhang X, Dong J, Gao W, Liu F, Zhao J . Association of chemokine ligand 5/chemokine receptor 5 gene promoter polymorphisms with diabetic microvascular complications: A meta-analysis. J Diabetes Investig. 2016; 7(2):212-8. PMC: 4773673. DOI: 10.1111/jdi.12397. View

Chen X, Wan Z, Geng T, Zhu K, Li R, Lu Q . Vitamin D Status, Vitamin D Receptor Polymorphisms, and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes: A Prospective Study. Diabetes Care. 2022; 46(2):270-277. DOI: 10.2337/dc22-0513. View

Hojs R, Ekart R, Bevc S, Hojs N . Markers of Inflammation and Oxidative Stress in the Development and Progression of Renal Disease in Diabetic Patients. Nephron. 2016; 133(3):159-62. DOI: 10.1159/000447434. View

10.

Singh R, Farooq S, Mannan A, Singh T, Najda A, Grazyna Z . Animal models of diabetic microvascular complications: Relevance to clinical features. Biomed Pharmacother. 2021; 145:112305. DOI: 10.1016/j.biopha.2021.112305. View

11.

Kwak S, Park K . Genetic Studies on Diabetic Microvascular Complications: Focusing on Genome-Wide Association Studies. Endocrinol Metab (Seoul). 2015; 30(2):147-58. PMC: 4508258. DOI: 10.3803/EnM.2015.30.2.147. View

12.

Fei X, Xing M, Wo M, Wang H, Yuan W, Huang Q . Thyroid stimulating hormone and free triiodothyronine are valuable predictors for diabetic nephropathy in patient with type 2 diabetes mellitus. Ann Transl Med. 2018; 6(15):305. PMC: 6123216. DOI: 10.21037/atm.2018.07.07. View

13.

Weng S, Chen W, Shen F, Wang P, Chen J, Liou C . Circulating Growth Differentiation Factor 15 Is Associated with Diabetic Neuropathy. J Clin Med. 2022; 11(11). PMC: 9180959. DOI: 10.3390/jcm11113033. View

14.

Wu D, Wu C, Zhong Y . The association between paraoxonase 1 activity and the susceptibilities of diabetes mellitus, diabetic macroangiopathy and diabetic microangiopathy. J Cell Mol Med. 2018; 22(9):4283-4291. PMC: 6111876. DOI: 10.1111/jcmm.13711. View

15.

Ebara S, Marumo M, Mukai J, Ohki M, Uchida K, Wakabayashi I . Relationships of oxidized HDL with blood coagulation and fibrinolysis in patients with type 2 diabetes mellitus. J Thromb Thrombolysis. 2017; 45(2):200-205. DOI: 10.1007/s11239-017-1594-x. View

16.

Plug T, Meijers J . Structure-function relationships in thrombin-activatable fibrinolysis inhibitor. J Thromb Haemost. 2016; 14(4):633-44. DOI: 10.1111/jth.13261. View

17.

Oikonomou D, Groener J, Cheko R, Kender Z, Kihm L, Fleming T . Genetic Polymorphisms of Antioxidant and Antiglycation Enzymes and Diabetic Complications. How Much Can we Learn from the Genes?. Exp Clin Endocrinol Diabetes. 2017; 126(1):7-13. DOI: 10.1055/s-0043-106442. View

18.

Saputro S, Pattanaprateep O, Pattanateepapon A, Karmacharya S, Thakkinstian A . Prognostic models of diabetic microvascular complications: a systematic review and meta-analysis. Syst Rev. 2021; 10(1):288. PMC: 8561867. DOI: 10.1186/s13643-021-01841-z. View

19.

Huang H, Luo Y, Wang Q, Zhang Y, Li Z, He R . as Potential Therapy for Diabetes and Microvascular Complications. Nutrients. 2023; 15(9). PMC: 10181411. DOI: 10.3390/nu15092031. View

20.

Grosso G, Vikerfors A, Woodhams B, Adam M, Bremme K, Holmstrom M . Thrombin activatable fibrinolysis inhibitor (TAFI) - A possible link between coagulation and complement activation in the antiphospholipid syndrome (APS). Thromb Res. 2017; 158:168-173. DOI: 10.1016/j.thromres.2017.06.028. View