scholarly journals Association of EPHX2 R287Q Polymorphism with Diabetic Nephropathy in Chinese Type 2 Diabetic Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Liang Ma ◽  
Meihua Yan ◽  
Xiaomu Kong ◽  
Yongwei Jiang ◽  
Tingting Zhao ◽  
...  

The aim of this study was to investigate the relationship between EPHX2 rs751141 (R287Q polymorphism) and diabetic nephropathy (DN) in Chinese type 2 diabetes (T2D). This case-control study explored the association between EPHX2 rs751141 and DN in a total of 870 Chinese T2D patients (406 T2D patients with DN and 464 T2D patients without DN). DNA was extracted from peripheral leukocytes of the patients and rs751141 was genotyped. The A allele frequency of rs751141 was significantly lower in DN patients (20.94%) compared with non-DN controls (27.8%) (P=0.001), and the A allele of rs751141 was associated with a significantly lower risk of DN after adjustment for multiple covariates in the additive genetic model (OR = 0.68, 95% CI = 0.52–0.88, P=0.004). Significant association between rs751141 and homocysteine (Hcy) level on the risk of DN was observed, indicating that in patients with the highest Hcy levels, the A allele showed marked association with lower risk of DN in all three genetic models. In conclusion, the A allele of exonic polymorphism in EPHX2 rs751141 is negatively associated with the incidence of DN in the Chinese T2D population, which could be modulated by Hcy level status.

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Liang Ma ◽  
Yongwei Jiang ◽  
Xiaomu Kong ◽  
Meihua Yan ◽  
Tingting Zhao ◽  
...  

The aim of this study was to investigate the relationship between the combined effect of MTHFR C677T (rs1801133) and EPHX2 G860A (rs751141) polymorphism and ischemic stroke in Chinese T2DM patients. This case-control study included a total of 626 Chinese T2DM patients (236 T2DM patients with ischemic stroke and 390 T2DM patients without ischemic stroke). The rs1801133 and rs751141 were genotyped using real-time polymerase chain reaction. Statistical analysis was performed with SPSS 17.0. Results showed that the combined effect of MTHFR TT and EPHX2 GG or GA + AA genotype has a higher risk of ischemic stroke compared with the control group (combined effect of MTHFR CC and EPHX2 GA + AA genotypes; OR = 3.46 and OR = 3.42, resp.; P=.001 and P=.002, resp.). The A allele showed marked association with a lower risk of ischemic stroke in patients with the lowest Hcy levels under additive, recessive, and dominant genetic models (OR = 0.45, OR = 0.11, and OR = 0.44, resp.; P=.002, P=.035, and P=.008, resp.), which was not observed in medium or high Hcy level groups. In conclusion, the T allele of rs1801133 and the G allele of rs751141 may be risk factors of ischemic stroke in the Chinese T2DM population.


2021 ◽  
Author(s):  
José Juan Sánchez-Hidalgo ◽  
Juan Antonio SUÁREZ-CUENCA ◽  
José Juan Lozano-Nuevo ◽  
Víctor Hugo García-López ◽  
María Graciela Leal-Gutiérrez ◽  
...  

Abstract Background Albumin, along with other proteins, is abnormally eliminated via the urine during early stages of diabetic nephropathy. Moreover, endothelial dysfunction (ED) accompanying early diabetic nephropathy may develop even before microalbuminuria is detectable. Transferrin has a molecular weight comparable to albumin, and transferrinuria and microalbuminuria in a 24-hour urine sample may comparably reflect early diabetic nephropathy. However, transferrin physiochemical properties may be related with ED, but these have not been elucidated yet. This case-control study was aimed to evaluate relation between ED and urinary transferrin concentration before early diabetic nephropathy is present. Methods Patients were enrolled from two study sites in Mexico City: Ticoman General Hospital to evaluate control patients; and Dr. Manuel Gonzalez Rivera Specialized Clinic for the Management of the Diabetic Patient for case patients. All patients provided written informed consent. The primary endpoint was the correlation between urinary transferrin concentration and endothelial dysfunction measured in type 2 diabetic patients without albuminuria. ED was evaluated by ultrasonographic validated measurements, which included carotid intima-media thickness (CIMT) and flow mediated dilation (FMD). A power calculation, to detect a statistical difference, with a p value of 0.05, mandated a sample of 60 patients. The patients were tested for serum biomarkers such as glycated hemoglobin, creatinine, cholesterol, triglycerides, and urinary dipstick for albuminuria and urinary tract infection; using inclusion, exclusion and elimination criteria as described. Results The group with type 2 diabetes was older and showed higher serum transferrin and lower urinary transferrin values. Likewise, the group with type 2 diabetes showed subclinical atherogenic risk characterized by lower FMD and higher CIMT and ABI values. Risk factors associated to endothelial dysfunction measured by CIMT were time from diagnosis of diabetes, insulin resistance, dyslipidemia, and male sex. Hba1c and time since diabetes diagnosis correlated both for risk associated to FMD and CIMT. CIMT was the only factor correlated with urinary transferrin values. Conclusion Urinary transferrin correlated to subclinical endothelial dysfunction measured by CIMT in type 2 diabetic patients without nephropathy and can be used to test for early nephropathy in patients without albuminuria.


2021 ◽  
Author(s):  
José Juan Sánchez-Hidalgo ◽  
Juan Antonio SUÁREZ-CUENCA ◽  
José Juan Lozano-Nuevo ◽  
Vìctor Hugo García-López ◽  
María Graciela Leal-Gutierrez ◽  
...  

Abstract Background Albumin, along with other proteins, is abnormally eliminated via the urine during early stages of diabetic nephropathy. Moreover, endothelial dysfunction (ED) accompanying early diabetic nephropathy may develop even before microalbuminuria is detectable. Transferrin has a molecular weight comparable to albumin, and transferrinuria and microalbuminuria in a 24-hour urine sample may comparably reflect early diabetic nephropathy. However, transferrin physiochemical properties may be related with ED, but these have not been elucidated yet. This case-control study was aimed to evaluate relation between ED and urinary transferrin concentration before early diabetic nephropathy is present. Methods Patients were enrolled from two study sites in Mexico City: Ticoman General Hospital to evaluate control patients; and Dr. Manuel Gonzalez Rivera Specialized Clinic for the Management of the Diabetic Patient for case patients. All patients provided written informed consent. The primary endpoint was the correlation between urinary transferrin concentration and endothelial dysfunction measured in type 2 diabetic patients without albuminuria. ED was evaluated by ultrasonographic validated measurements, which included carotid intima-media thickness (CIMT) and flow mediated dilation (FMD). A power calculation, to detect a statistical difference, with a p value of 0.05, mandated a sample of 60 patients. The patients were tested for serum biomarkers such as glycated hemoglobin, creatinine, cholesterol, triglycerides, and urinary dipstick for albuminuria and urinary tract infection; using inclusion, exclusion and elimination criteria as described. Results The group with type 2 diabetes was older and showed higher serum transferrin and lower urinary transferrin values. Likewise, the group with type 2 diabetes showed subclinical atherogenic risk characterized by lower FMD and higher CIMT and ABI values. Risk factors associated to endothelial dysfunction measured by CIMT were time from diagnosis of diabetes, insulin resistance, dyslipidemia, and male sex. Hba1c and time since diabetes diagnosis correlated both for risk associated to FMD and CIMT. CIMT was the only factor correlated with urinary transferrin values. Conclusion Urinary transferrin correlated to subclinical endothelial dysfunction measured by CIMT in type 2 diabetic patients without nephropathy and can be used to test for early nephropathy in patients without albuminuria.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
José Juan Sánchez-Hidalgo ◽  
Juan Antonio Suárez-Cuenca ◽  
José Juan Lozano-Nuevo ◽  
Víctor Hugo García-López ◽  
María Graciela Leal-Gutiérrez ◽  
...  

Abstract Background Albumin, along with other proteins, is abnormally eliminated via the urine during early stages of diabetic nephropathy. Moreover, endothelial dysfunction (ED) accompanying early diabetic nephropathy may develop even before microalbuminuria is detectable. Transferrin has a molecular weight comparable to albumin, whereas transferrinuria and microalbuminuria in a 24-h urine sample may comparably reflect early diabetic nephropathy. Whereas transferrin metabolism is related with ED during very early diabetic nephropathy has not been elucidated yet. This case–control study aimed to evaluate the relation between ED and urine transferrin, even before early diabetic nephropathy is present. Methods Patients were enrolled from two study sites in Mexico City: Ticomán General Hospital (healthy controls); and a Specialized Clinic for the Management of the Diabetic Patient (cases). All patients provided written informed consent. The primary endpoint was the correlation between urinary transferrin concentration and ED measured in type 2 diabetic patients without albuminuria. ED was evaluated by ultrasonographic validated measurements, which included carotid intima-media thickness (CIMT) and flow mediated dilation (FMD). Plasma biomarkers included glycated hemoglobin, creatinine, cholesterol and triglycerides, as well as urine albumin, transferrin and evidence of urinary tract infection. Results Sixty patients with type 2 Diabetes Mellitus (t2DM; n = 30) or without t2DM (n = 30), both negative for microalbuminuria, were recruited. The group with t2DM were older, with higher values of HbA1c and higher ED. This group also showed significant differences in urine transferrin and urine/plasma transferrin ratio, as compared with healthy controls (14.4 vs. 18.7 mg/mL, p = 0.04, and 74.2 vs. 49.5; p = 0.01; respectively). Moreover, urine transferrin correlated with higher CIMT values (r = 0.37, p = 0.04), being particularly significant for t2DM population. CIMT also correlated with time from t2DM diagnosis (r = 0.48, p < 0.001) and HbA1c (r = 0.48; p < 0.001). Conclusion Urine transferrin correlated with subclinical atherogenesis in patients with t2DM without renal failure, suggesting its potential to identify cardiovascular risk in patients at very early nephropathy stage without microalbuminuria.


2013 ◽  
Vol 16 (3) ◽  
pp. 486 ◽  
Author(s):  
Tingting Zhao ◽  
Xiaoguang Lu ◽  
Neal M Davies ◽  
Yuewen Gong ◽  
Jingzhen Guo ◽  
...  

Purpose. The assessment of the clinical significance of chondroitin sulfate in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) for the detection of the relationship between chondroitin sulfate (CS) structure and disease. Methods. Healthy control (n=15), type 2 diabetic patients with normalbuminuria (n=12), and patients with microalbuminuria (n=13) were enrolled in the study. Total sulfated glycosaminoglycans (GAGs) concentration in the first morning urine was evaluated by 1,9-dimethylmethylene blue method and the composition was determined by agarose gel electrophoresis. Urinary chondroitin sulfate was quantified by a combination of treatment with specific lyase digestions and separation of products by SAX-HPLC. Results: GAGs concentration significantly increased in diabetic patients with microalbuminuria compared to diabetic patients with normalbuminuria. Qualitative analysis of urinary GAGs revealed the presence of chondroitin sulfate, heparan sulfate, and low-sulphated chondroitin sulphate-protein complex (LSC-PG). There was a decrease in CS and an increase in LSC-PG in the urine of patients with diabetes compared to healthy controls. Moreover, in diabetic patients, chondroitin sulfate contains more 6-sulfated disaccharide and less 4-sulfated disaccharide. There was a statistically significant difference in ratio of 6-sulfated disaccharide to 4-sulfated disaccharide among the three groups. Conclusions: GAGs were significantly increased in diabetic patients with microalbuminuria. The levels of urinary GAGs, ratio of LSC-PG/CS, as well as ratio of 6-sulfated to 4-sulfated disaccharides could be useful markers for diagnosis of patients with diabetic nephropathy.   This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.


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