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Genetic polymorphisms predisposing to hyperhomocysteinemia in cardiac transplant patients.
Transpl Int 2005; 18(1):29-35TI

Abstract

Genetic determinants for high homocysteine (Hcy) levels are now well known. We studied several single nucleotide polymorphisms (SNP) in Hcy-regulating genes [methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C; methionine synthase (MS) A2756G; methionine synthase reductase (MTRR) A66G] in relation to total plasma Hcy levels, transplant coronary artery disease and thromboembolic episodes in 84 heart transplant patients, and we compared the incidence of these polymorphisms with those in a healthy adult controls. At least one copy of the G allele of the MTRR A66G SNP was found in a significantly greater proportion of cardiac transplant (CTX) recipients compared with controls (94.0% vs. 79.9% respectively). None of the SNP analyzed were correlated with total Hcy plasma levels or the presence of transplant coronary artery disease. However, MS A2756G was significantly associated with cobalamin levels (AA genotype: 290 +/- 122 pmol/l; AG: 381 +/- 151 pmol/l and GG: 415 +/- 100 pmol/l), as was MTRR A66G (AA: 478 +/- 219 pmol/l, AG: 306 +/- 124 pmol/l and GG: 306 +/- 123 pmol/l). MTRR A66G was also correlated with serum folate. No association was found with thromboembolic events. In conclusion, there was a significant difference in the frequency of the G allele genotype of the MTRR A66G in CTX patients versus controls. Differences in cobalamin and folate levels with the MTRR A66G and MS A2756G polymorphisms were noted. Thus, SNP in Hcy-regulating genes may be important determinants of vitamin metabolism in CTX, raising the question of increased vitamin requirements to minimize increased plasma Hcy in this high-risk group.

Authors+Show Affiliations

Department of Medicine, Toronto General Hospital and University of Toronto, Toronto, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15612980

Citation

Miriuka, Santiago G., et al. "Genetic Polymorphisms Predisposing to Hyperhomocysteinemia in Cardiac Transplant Patients." Transplant International : Official Journal of the European Society for Organ Transplantation, vol. 18, no. 1, 2005, pp. 29-35.
Miriuka SG, Langman LJ, Evrovski J, et al. Genetic polymorphisms predisposing to hyperhomocysteinemia in cardiac transplant patients. Transpl Int. 2005;18(1):29-35.
Miriuka, S. G., Langman, L. J., Evrovski, J., Miner, S. E., D'Mello, N., Delgado, D. H., ... Cole, D. E. (2005). Genetic polymorphisms predisposing to hyperhomocysteinemia in cardiac transplant patients. Transplant International : Official Journal of the European Society for Organ Transplantation, 18(1), pp. 29-35.
Miriuka SG, et al. Genetic Polymorphisms Predisposing to Hyperhomocysteinemia in Cardiac Transplant Patients. Transpl Int. 2005;18(1):29-35. PubMed PMID: 15612980.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic polymorphisms predisposing to hyperhomocysteinemia in cardiac transplant patients. AU - Miriuka,Santiago G, AU - Langman,Loralie J, AU - Evrovski,Jovan, AU - Miner,Steven E S, AU - D'Mello,Nisha, AU - Delgado,Diego H, AU - Wong,Betty Y L, AU - Ross,Heather J, AU - Cole,David E C, PY - 2004/12/23/pubmed PY - 2005/7/7/medline PY - 2004/12/23/entrez SP - 29 EP - 35 JF - Transplant international : official journal of the European Society for Organ Transplantation JO - Transpl. Int. VL - 18 IS - 1 N2 - Genetic determinants for high homocysteine (Hcy) levels are now well known. We studied several single nucleotide polymorphisms (SNP) in Hcy-regulating genes [methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C; methionine synthase (MS) A2756G; methionine synthase reductase (MTRR) A66G] in relation to total plasma Hcy levels, transplant coronary artery disease and thromboembolic episodes in 84 heart transplant patients, and we compared the incidence of these polymorphisms with those in a healthy adult controls. At least one copy of the G allele of the MTRR A66G SNP was found in a significantly greater proportion of cardiac transplant (CTX) recipients compared with controls (94.0% vs. 79.9% respectively). None of the SNP analyzed were correlated with total Hcy plasma levels or the presence of transplant coronary artery disease. However, MS A2756G was significantly associated with cobalamin levels (AA genotype: 290 +/- 122 pmol/l; AG: 381 +/- 151 pmol/l and GG: 415 +/- 100 pmol/l), as was MTRR A66G (AA: 478 +/- 219 pmol/l, AG: 306 +/- 124 pmol/l and GG: 306 +/- 123 pmol/l). MTRR A66G was also correlated with serum folate. No association was found with thromboembolic events. In conclusion, there was a significant difference in the frequency of the G allele genotype of the MTRR A66G in CTX patients versus controls. Differences in cobalamin and folate levels with the MTRR A66G and MS A2756G polymorphisms were noted. Thus, SNP in Hcy-regulating genes may be important determinants of vitamin metabolism in CTX, raising the question of increased vitamin requirements to minimize increased plasma Hcy in this high-risk group. SN - 0934-0874 UR - https://www.unboundmedicine.com/medline/citation/15612980/Genetic_polymorphisms_predisposing_to_hyperhomocysteinemia_in_cardiac_transplant_patients_ L2 - http://link.springer.com/article/10.1111/j.1432-2277.2004.00021.x DB - PRIME DP - Unbound Medicine ER -