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Letters to the Editor |
The Vascular Biology Unit, James Cook University, Townsville, Queensland, Australia
aAddress correspondence to this author at: The Vascular Biology Unit, James Cook University, Townsville, Queensland 4811, Australia. Fax 61-7-4796-1401; e-mail Jonathan.Golledge{at}jcu.edu.au.
To the Editor:
We read with interest the article by Pastore et al. (1), who demonstrated that the effect of folate and vitamin B12 treatment in reducing total plasma homocysteine (tHcy) concentration is dependent on methylenetetrahydrofolate reductase (MTHFR) genotype in patients with end-stage renal failure. Their findings may partially explain the difficulty in demonstrating a benefit of vitamin supplementation in reducing cardiovascular end-point, as treatment may have to be tailored to subgroups of patients such as those with the MTHFR T allele (2)(3). Although tHcy concentrations are much lower in individuals with normal renal function, they still predict subsequent cardiovascular events (4).
We investigated the value of MTHFR genotype for potentially differentiating vitamin therapy groups in patients presenting with peripheral vascular disease. A total of 217 patients, presenting with abdominal aortic aneurysm (n = 80), carotid artery disease (n = 72), or symptomatic lower limb ischemia (n = 65), were screened for atherosclerotic risk factors, as described previously (5). MTHFR genotype was assessed by the homogeneous MassEXTEND (hME; Sequenom) assay, which uses primer amplification in combination with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry to identify extension products (6). tHcy values in our patients were low (range, 1–40 µmol/L) and not significantly affected by MTHFR genotype (Table 1
). Interestingly, patients with the TT C677T MTHFR genotype had lower serum HDL concentrations. The primary determinants of tHcy were folate and vitamin B12 status. The mean (SD) concentrations of tHcy by folate and vitamin B12 tertiles were 15.34 (5.60), 12.10 (4.46), 11.17 (4.09) (P = 0.003) and 14.99 (5.98), 12.39 (3.27), and 11.24 (4.90) (P = 0.02), respectively. Our findings are in keeping with those from a recent study (7) and suggest that assessment of vitamin B12 and folate status may best predict those patients with peripheral vascular disease requiring intervention to reduce tHcy concentrations.
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Acknowledgments
The authors are supported by funding from the National Health and Medical Research Council (279408 and 379600) and from the National Institutes of Health (R01 HL080010-01). We thank Dr. P. Kanowski and staff at Northern Pathology, Townsville, for help with the serum assays.
References
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