Methyltetrahydrofolate reductase C677T gene mutation and hyperhomocysteinemia as a novel risk factor for diabetic nephro
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ORIGINAL PAPER
Methyltetrahydrofolate reductase C677T gene mutation and hyperhomocysteinemia as a novel risk factor for diabetic nephropathy Kubilay Ukinc Æ Halil Onder Ersoz Æ Caner Karahan Æ Cihangir Erem Æ Selcuk Eminagaoglu Æ Arif Bayram Hacihasanoglu Æ Mustafa Yilmaz Æ Mustafa Kocak
Received: 11 February 2009 / Accepted: 4 June 2009 / Published online: 14 July 2009 Ó Humana Press 2009
Abstract Hyperhomocysteinemia is a well-defined risk factor for endothelial dysfunction and atherosclerosis. A point mutation (677 C-T) of MTHFR gene results in a significant increase at plasma homocysteine levels. In this study we aimed to evaluate the effects of MTHFR gene mutation and consequent hyperhomocysteinemia on the development of diabetic microvascular complications in comparison with the other defined risk factors. Diabetic patients without a history of macrovascular complication or overt nephropathy enrolled into the study. The presence of MTHFR 677 C-T point mutation was evaluated by Real-Time PCR technique by using a LightCycler. MTHFR heterozygous mutation was present in 24 patients over 52. Patients with diabetes were divided into two groups according to the presence of MTHFR gene mutation. Both groups were well matched regarding age and diabetes duration. Metabolic parameters,
Part of this study was presented in 41st Annual Meeting of EASD (Athens–2005) printed as an abstract in Diabetologia 48(S1): A370, 2005. K. Ukinc (&) C¸anakkale Onsekiz Mart Universitesi, Tıp Fakultesi, Endokrinoloji ve Metabolizma Hastaliklari BD, C¸anakkale 17020, Turkey e-mail: [email protected] H. O. Ersoz C. Erem A. B. Hacihasanoglu M. Kocak Department of Endocrinology and Metabolism, Karadeniz Technical University, Trabzon, Turkey C. Karahan S. Eminagaoglu Department of Biochemistry, Karadeniz Technical University, Trabzon, Turkey M. Yilmaz Department of Hematology, Karadeniz Technical University, Trabzon, Turkey
plasma homocysteine, microalbuminuria, folic acid, and vitamin B12 levels were also studied. Presence of neuropathy and retinopathy were evaluated by specific tests. Duration of diabetes, BMI, systolic and diastolic blood pressure, plasma CRP, HbA1c, and lipid levels were not different between the two groups. Plasma homocysteine (12.89 ± 1.74 and 8.98 ± 1.91 lmol/l; P \ 0.0001) and microalbuminuria levels (73.40 ± 98.15 and 29.53 ± 5.08 mg/day; P = 0.021) were significantly higher in the group with MTHFR gene mutation while creatinine clearance levels (101.1 ± 42.6 and 136.21 ± 51.50 ml/min; P = 0.008) were significantly lower. Sixteen over 22 (73%) of the patients with diabetic nephropathy had MTHFR gene mutation, while this was only 27% (8 over 30) in normoalbuminuric patients (P = 0.017). There was a significant correlation of plasma homocysteine level with microalbuminuria (r = 0.54; P = 0.031) in the patients with diabetic nephropathy who had C677T polymorphism. We did not find any specific association of MTHFR gene mutation and hyperhomocysteinemia with retinopathy or neuropathy. Keywords MTHFR C677T mutati
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