[Some aspects of homocysteine metabolism in hemodialysis patients].
Homocysteine (Hcy) is a non-protein forming sulfur amino acid, synthesised from methionine (Met), whose metabolism is at the junction of two metabolic pathways: remethylation and transsulfuration. Increased Hcy serum concentration is a well established independent risk factor of cardiovascular diseases and a known feature of end stage renal disease. Hcy plasma level is influenced by folate, vitamin B6 and genetic factors. Mutation C677T in gene encoding methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in Hcy remethylation has been associated with elevated Hcy in homozygous carriers (TT genotype). Several amino acids take part in metabolism of Hcy. There are abnormalities of concentration of the non essential and essential of amino acids in serum of patients treated with hemodialysis (HD). It is possible that these abnormalities of amino acids can change the Hcy metabolism. The aim of this study was the evaluation of some aspects of Hcy metabolism. We examined the MTHFR gene polymorphism and its relationship with plasma Hcy concentration. The plasma levels of total amino acids and amino acids connected with Hcy metabolism: methionine (Met), seryne (Ser), cysteine (Cyst) and tauryne (Tau) were evaluated in hemodialysis patients. The study was conducted in 71 (35 male, 36 female) patients, mean age 56.2 +/- 12.4 years. They were dialysed for a mean duration of 87.7 +/- 84.7 months (range 2-302). The control group (CG) in which Hcy and amino acids levels were examined consisted of 12 healthy subjects. Serum (EDTA) Hcy levels were measured by EIA-Hcy ELISA kit. The MTHFR gene polymorphism was evaluated by means of the polymerase chain reaction (PCR). The amino acids were measured by chromatography in amino acid analyser AAA 400. Mean concentration of Hcy was significantly higher in patients than in CG (31.1 +/- 9.1 vs 11.9 +/- 2.9 mumol/L; p < 0.01). Genotype frequencies in patients were: 42.8% for CC, 48.5% for CT and 8.7% for TT. Mean concentration of Hcy were similar in above genotype groups: 31.2 +/- 9.4; 30.7 +/- 10.7; 32.8 +/- 5.1 mumol/L, respectively. We did not find any correlation between Hcy level and the mutation in gene coding for MTHFR in our study group of patients. Mean total amino acid concentrations were significantly lower in plasma patients than in CG: 3624.48 +/- 140.32 vs 4454.45 +/- 774.91 mumol/L; p < 0.05. Mean plasma level of Tau was significantly lower in patients than in CG: 93.01 +/- 43.73 vs 286.75 +/- 57.02 mumol/l; p < 0.01. Also mean plasma level of Ser was significantly lower in patients than in CG; 125.71 +/- 24.25 vs 233.61 +/- 44.55 mumol/L; p < 0.01. Mean concentration of Cys were significantly higher in hemodialysis patients than in CG: 100.82 +/- 43.53 vs 31.31 +/- 21.31 mumol/L; p < 0.01. Mean Met concentrations were not significantly different between two studied groups. We found significant positive correlation between plasma Hcy levels and plasma Cys level (r = 0491; p < 0.05). Also there was a significant positive correlation between plasma Hcy level and duration of hemodialysis (r = 5411; p < 0.05). We concluded that in our studied population of hemodialysis patients there was no significant association between mutation in the gene coding for MTHFR and hyperhomocysteinemia and hypercysteinemia. There are abnormalities of plasma level of amino acids which are take part in Hcy metabolism in hemodialysis patients.
Bednarek-Skublewska
Anna
A
Katedra i Klinika Nefrologii AM, Lublinie.
Buraczyńska
Monika
M
Wawrzycki
Sławomir
S
Baranowicz-Gaszczyk
Iwona
I
Ksiazek
Andrzej
A
D000328:Adult; D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D006435:Renal Dialysis / Q000379:methods*
D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)