Academic journal article Iranian Journal of Public Health

Different Risk Indictors of Diabetic Nephropathy in Transforming Growth Factor-Beta1 T869C CC/CT Genotype and TT Genotype

Academic journal article Iranian Journal of Public Health

Different Risk Indictors of Diabetic Nephropathy in Transforming Growth Factor-Beta1 T869C CC/CT Genotype and TT Genotype

Article excerpt


Diabetic Nephropathy (DN) is one of the most conventional microvascular complications of diabetes mellitus. Approximately 30%-40% of all patients with diabetes develop DN and it is the primary leading cause of end stage renal disease (ESRD) (1). Meanwhile, the ESRD is the main cause of death in type 2 diabetes mellitus (T2DM). Therefore, it is important to prevent diabetes developing into DN (2, 3).

Many factors, such as hypertension, hyperglycemia, the accumulation of advanced glycation products, dyslipidemia, and albuminuria/proteinuria, increase the risk of DN. Besides, diabetic patients may have increased susceptibility to DN due to genetic factors (4-6), such as transforming growth factor-β1 (TGF-β1) T869C (Leu 10 Pro) gene polymorphism. Transforming growth factor-beta (TGF-β) is a multifunctional regulator that modulates cell proliferation, differentiation, apoptosis, adhesion and migration of various cell types and induces the production of extracellular matrix proteins (7). "It is synthesized by many renal cell types and exerts its biological functions through a variety of signalling pathways, including the Smad and MAPK pathways" (8). "In renal diseases, TGF-β is upregulated and induces renal cells to produce extracellular matrix proteins leading to glomerulosclerosis as well as tubulointerstitial fibrosis, which ultimately result in renal dysfunction" (9). T869C gene polymorphism was notable different between patients with DN and diabetic patients without DN, and the DN group had higher frequency of CC/CT genotype than the diabetes without DN group (5). Similar results were also found in other studies (10, 11). These conclusions were in line with our previous findings (12).

T869C gene polymorphism has not yet been studied in prospective cohort study in T2DM patients. We thereby conducted a study to confirm whether T869C gene polymorphism contributes to the established predictor of DN, and secondly, to find out different risk factors to provide a better and possibly different treatment for susceptible populations (T869C CC/CT genotype) and non- susceptible populations (T869C TT genotype).

Materials and Methods

Study patients

This was a prospective, observational cohort study. All of the patients admitted met the diagnostic criteria of DM proposed by WHO in 1999, the Chinese Medical Association, and the diagnostic criteria of T2DM in "China Guideline for Diabetes (Trial Version)"(13), and DN was defined in accordance with the internationally recognized Mogensen staging criteria (14). All of the cases were recruited from January 2010 to May 2011, diagnosed as T2DM. Patients were followed every half year until May 2013. All of the patients were recruited in the Hangzhou Red Cross Hospital, with a DM duration >4 yr and no limit of sex and age. Individuals with a history of malignancy, receiving a kidney transplant, cerebral vascular accidents, or myocardial infarction were eliminated from this study. A total of 251 patients were enrolled finally.

Informed consent was obtained from all the patients before enrollment in the study. This study was performed and approved by the institutional Ethics Committee of our hospital.

Data Collection and laboratory measurements

The following demographic and clinical data were collected for each patient: age, gender, height, weight, primary renal disease, duration of DM, smoking status, drinking status, glycated hemoglobin (HbA1c) level, and comorbid conditions including hypertension, hyperlipemia. Fasting blood samples were checked for glucose, hemoglobin (HbA1c), and lipids. Arterial blood pressure was measured using a standard sphygmomanometer and hypertension was recorded if the patient was taking antihypertensive drugs or had two separated measured blood pressures >140/90 mmHg. Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were measured by enzymatic method. Hyperlipidemic subjects had total cholesterol ≥200 mg/dL and LDL-C ≥100 mg/dL. …

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