Prevalence of methylenetetrahydrofolate gene (MTHFR) C677T polymorphism among chronic hemodialysis patients and its association with cardiovascular disease: a cross-sectional analysis
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Cardiovascular disease (CVD) remains the main cause of morbidity and mortality in end stage renal disease (ESDR) patients. A common C–T mutation at nucleotide position 677 (C677T) has been identified in the gene coding for methylenetetrahydrofolate reductase (MTHFR), which is involved in the remethylation of homocysteine (Hcy). The C677T mutation decreases MTHFR activity, tends to increase Hcy concentrations in individuals who are homozygous for the T/T genotype, and may predispose to CVD. Recent reports suggested that the T/T genotype may predispose type 2 diabetic and hypertensive patients to the development of progressive renal insufficiency. The aim of this cross-sectional study is to analyze the prevalence of the MTHFR C677T gene polymorphism among a group of chronic dialysis patients in comparison to age- and gender-matched controls. We also examined the possible association between CVD and MTHFR gene mutation in this group of patients.
Patients and methods
Fifty chronic hemodialysis patients were included in the study. They were 29 males and 21 females with a mean age of 41.57 ± 11.76 years. Three patients (6%) were diabetic (type 2). Mean duration of dialysis was 6.4 ± 3.2 years (range 1–15 years). CVD was defined as being present if there was a medical history of coronary artery disease, cerebrovascular stroke or transient ischemic attacks. MTHFR C677T gene polymorphism was analyzed by PCR in order to discriminate between homozygous (C/C and T/T) and heterozygous (C/T) genotypes. We also measured serum vitamin B12, folate, total plasma Hcy (tHcy), lipid profile and serum albumin concentrations in the study group. Thirty healthy subjects (16 males and 14 females with mean age of 37.42 ± 7.63 years) served as healthy controls.
Thirteen patients (26%) experienced at least one cardiovascular event: two (4%) had a history of ischemic cerebrovascular disease, 13 (26%) had coronary artery disease, and one patient (2%) had myocardial infarction. The C677T mutation of MTHFR was not found to be different in hemodialysis patients and healthy controls. Thirty dialysis patients (60%) and 19 healthy subjects (63.33%) had only the wild-type allele (C/C), 16 dialysis patients (32%) and nine healthy controls (30%) had one T allele (C/T), and four dialysis patients (8%) and two healthy controls (6.67%) had two copies (T/T) of the T allele. There were no differences between patients with the three different MTHFR genotypes (C/C, C/T, T/T) regarding cardiovascular events or cardiovascular risk factors. Age, gender, percentages of diabetic and hypertensive patients, serum folate, vitamin B12, lipid profile, and tHcy levels were not significantly different between the three groups (P > 0.05). Hemodialysis patients with CVD were significantly older compared to those without CVD (P = 0.02). Diabetes status was significantly associated with cardiovascular events (P = 0.01).
In the dialysis population that we studied, MTHFR C677T gene polymorphism occurred in a pattern similar to that seen for age- and gender-matched healthy controls. No significant association was detected between the T/T genotype and CVD in dialysis patients. Plasma total homocysteine levels were not affected by mutation of the gene coding for MTHFR, and this may be explained by the normal serum folate and vitamin B12 levels found in the study group.
KeywordsMethylenetetrahydrofolate reductase gene polymorphism Hemodialysis Cardiovascular disease Hyperhomocysteinemia
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