BACKGROUND: Diabetic nephropathy develops in 20-30% of patients with non-insulin dependent diabetes mellitus (NIDDM). Poor glycemic control, hypertension and duration of diabetes are known as risk factors for the development of diabetic nephropathy and there is high prevalence of diabetic nephropathy in the patients who have familial history of diabetic nephropathy, so it has been assumed that genetic factor is associated with the background of its occurences. Recently it has been observed that a cytosine to thymidine substitution of the methylenetetrahydrofolate reductase (MTHFR) gene at nucleotide 677 (C677T) was related to diabetic nephropathy in patients with NIDDM and MTHFR gene polymorphism was also known to predispose to vascular disease. This study was performed to investigate whether MTHFR gene polymorphism is associated with the development of diabetic nephropathy and macrovascular disease in NIDDM patients. METHODS: The study population consisted of 243 NIDDM patients (duration> OR = 10 years). Nephropathy was defined by 24 hour urinary protein excretion of more than 500 mg. The MTHFR gene fragment was extracted using the polymerase chain reaction. The presence of the mutation was identified by HinfI digestion, which cuts at the mutation site, followed by 2.5% metaphore agarose electrophoresis and ethidium bromide staining. Statistical differences in genotype distribution and allele frequencies among the groups were assessed by the chi-square test. RESULTS: There was no difference in clinical characteristics except the prevalence of hypertension and diabetic retinopathy between nephropathy group and non-nephropathy group. The data do not show any difference of genotype distribution or allele frequencies between patients with or without diabetic nephropathy and macrovascular disease CONCLUSION: With the above results, it is assumed that there are no significant relationships among MTHFR gene polymorphism, diabetic nephropathy, and macrovascular disease.
Cytosine ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Diabetic Nephropathies* ; Diabetic Retinopathy ; Digestion ; Electrophoresis ; Ethidium ; Fibrinogen ; Gene Frequency ; Genotype ; Humans ; Hypertension ; Metaphor ; Methylenetetrahydrofolate Reductase (NADPH2) ; Polymerase Chain Reaction ; Prevalence ; Risk Factors* ; Sepharose ; Thymidine ; Vascular Diseases

Recombinant human erythropoietin(r-HuEPO) is the mainstay of anemia therapy in patient with end stage renal disease(ESRD), but the use of r-HuEPO is primarily limited by its high cost. So, it encourages any strategies that potentially enhance the erythropoietic response. However, studies designed to assess whether androgens would enhance the response to r-HuEPO were inconclusive. While androgens may be less expensive and may improve several nutritional parameters, their potential adverse effects discourage usage. We carried out a prospective study to examine the effect of low-dose androgen in combination with subcutaneous r-HuEPO on anemia and nutritional paramenters in hemodialysis patients. Twenty-four hemodialysis patients with hematocrit <24% or hemoglobin <8.0g/dL were randomly assigned into two groups. Group A(n=12) received 2000U r-HuEPO subcutaneously twice a week for six months. Group B(n=12) received the same dose of r-HuEPO plus nandrolone decanoate 100mg intramuscularly biweekly. Anthropometry, albumin, cholesterol, prealbumin, and transferrin were measured as nutritional parameters. The groups showed no differences in baseline levels of the followings : Hemoglobin, hematocrit; transferrin saturation; serum ferritin; intact serum parathyroid hormon, Kt/V; vitamin B12, folate; nutritional parameters. At the completion of the study, both groups showed significant increase in hematocrit compared with baseline levels(group A 20.7+/-2.2% to 26.0+/-3.8%; group B : 21.5+/-3.5% to 30.1+/-2.8%). The mean hematocrit in group B was significantly higher than in group A after 4 month study period(p<0.05). Ten of 12 patients in group B achieved a target hematocrit of 30%, as compared with four of 12 patients in group A. Both groups didn't show significant changes in any nutritional parameters. No significant side effects of androgen were noted during this short-term study. We conclude that low-dose androgen in combination with subcutaneous r-HuEPO is effetive treatment on anemia in hemodialysis patients, but does not improve nutritional status.
Androgens ; Anemia* ; Anthropometry ; Cholesterol ; Erythropoietin* ; Ferritins ; Folic Acid ; Hematocrit ; Humans* ; Nandrolone ; Nutritional Status ; Prealbumin ; Prospective Studies ; Renal Dialysis* ; Transferrin ; Vitamin B 12