INCREASED EXPRESSION OF NITRIC OXIDE SYNTHASES IN HUMAN TYPE 2 DIABETIC NEPHROPATHY CORRELATES WITH CLINICAL RISK FACTORS OF DISEASE PROGRESSION

Type 2 diabetes mellitus (T2DM) is associated with a high incidence of nephropathy. The aim of this study was to investigate the association of a genetic polymorphism of carnosinase (CNDP1-D18S880and -rs2346061), endothelial nitric oxide synthase (NOS3-rs1799983), and manganese superoxide dismutase (MnSOD-rs4880) genes with the development of diabetic nephropathy among Malaysian type 2 diabetic patients. A case-control association study was performed using 652 T2DM patients comprising 227 Malays (without nephropathy = 96 and nephropathy = 131), 203 Chinese (without nephropathy = 95 and nephropathy = 108), and 222 Indians (without nephropathy = 136 and nephropathy = 86). DNA sequencing was performed for theD18S880ofCNDP1, while the rest were tested using DNA Sequenom MassARRAY to identify the polymorphisms. DNA was extracted from the secondary blood samples taken from the T2DM patients. The alleles and genotypes were tested using four genetic models, and the best mode of inheritance was chosen based on the leastpvalue. Thers2346061ofCNDP1was significantly associated with diabetic nephropathy among the Indians only with OR = 1.94 and 95% CI = (1.76–3.20) and fitted best the multiplicative model, whileD18S880was associated among all the three major races with the Malays having the strongest association with OR = 2.46 and 95% CI = (1.48–4.10), Chinese with OR = 2.26 and 95% CI = (1.34–3.83), and Indians with OR = 1.77 and 95% CI = (1.18–2.65) in the genotypic multiplicative model. The best mode of inheritance for bothMnSODandNOS3was the additive model. ForMnSOD-rs4880, the Chinese had OR = 2.8 and 95% CI = (0.53–14.94), Indians had OR = 2.4 and 95% CI = (0.69–2.84), and Malays had OR = 2.16 and 95% CI = (0.54–8.65), while forNOS3-rs1799983, the Indians had the highest risk with OR = 3.16 and 95% CI = (0.52–17.56), followed by the Chinese with OR = 3.55 and 95% CI = (0.36–35.03) and the Malays with OR = 2.89 and 95% CI = (0.29–28.32). The four oxidative stress-related polymorphisms have significant effects on the development of nephropathy in type 2 diabetes patients. The genes may, therefore, be considered as risk factors for Malaysian subjects who are predisposed to T2DM nephropathy.

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SP300CIRCULATING TNF RECEPTOR LEVELS AND RENAL DISEASE PROGRESSION IN PATIENTS WITH TYPE 2 DIABETIC NEPHROPATHY AND BLOCKADE OF THE RENIN ANGIOTENSIN SYSTEM

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfv191.20 ◽

2015 ◽

Vol 30 (suppl_3) ◽

pp. iii478-iii479

Author(s):

Gema Maria Fernandez Juarez ◽

Javier Villacorta Pérez ◽

Ernesto Martinez Martinez ◽

Victoria Cachofeiro ◽

Ana Tato ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Renal Disease ◽

Disease Progression ◽

Renin Angiotensin System ◽

Tnf Receptor ◽

Renal Disease Progression ◽

Angiotensin System ◽

Renin Angiotensin ◽

Type 2 Diabetic

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Genetic risk score for risk prediction of diabetic nephropathy in Han Chinese type 2 diabetes patients

Scientific Reports ◽

10.1038/s41598-019-56400-3 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Li-Na Liao ◽

Tsai-Chung Li ◽

Chia-Ing Li ◽

Chiu-Shong Liu ◽

Wen-Yuan Lin ◽

...

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Prediction Model ◽

Risk Prediction ◽

Genetic Risk Score ◽

Clinical Risk Factors ◽

Clinical Risk ◽

Conventional Risk Factors ◽

Diabetes Patients

AbstractWe evaluated whether genetic information could offer improvement on risk prediction of diabetic nephropathy (DN) while adding susceptibility variants into a risk prediction model with conventional risk factors in Han Chinese type 2 diabetes patients. A total of 995 (including 246 DN cases) and 519 (including 179 DN cases) type 2 diabetes patients were included in derivation and validation sets, respectively. A genetic risk score (GRS) was constructed with DN susceptibility variants based on findings of our previous genome-wide association study. In derivation set, areas under the receiver operating characteristics (AUROC) curve (95% CI) for model with clinical risk factors only, model with GRS only, and model with clinical risk factors and GRS were 0.75 (0.72–0.78), 0.64 (0.60–0.68), and 0.78 (0.75–0.81), respectively. In external validation sample, AUROC for model combining conventional risk factors and GRS was 0.70 (0.65–0.74). Additionally, the net reclassification improvement was 9.98% (P = 0.001) when the GRS was added to the prediction model of a set of clinical risk factors. This prediction model enabled us to confirm the importance of GRS combined with clinical factors in predicting the risk of DN and enhanced identification of high-risk individuals for appropriate management of DN for intervention.

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