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The effect of a common methylenetetrahydrofolate reductase mutation on levels of homocysteine, folate, vitamin B12 and on the risk of premature atherosclerosis.
Atherosclerosis 1998; 141(1):161-6A

Abstract

An increased total plasma homocysteine level is an established risk factor for atherosclerotic vascular disease. The plasma level of homocysteine is influenced by both environmental and genetic factors. An important genetic determinant of plasma homocysteine is a common amino acid dimorphism (Ala222Val) in the methylenetetrahydrofolate reductase (MTHFR) gene. Individuals homozygous for the Val allele have significantly higher homocysteine levels than those with an Ala/Val or Ala/Ala genotype. Moreover, the Val/Val genotype has been claimed to be a strong genetic risk factor for atherosclerosis. The aim of the present study is: (1) to determine the risk associated with the MTHFR dimorphism by comparing the genotype distribution in patients with premature atherosclerosis with that in a group of healthy controls; and (2) to investigate the relationship between the MTHFR genotype and parameters of homocysteine metabolism. The patient group consisted of 257 consecutive referred individuals with angiographically proven premature (<50 years of age) arterial disease (coronary, and/or peripheral vascular disease). A total of 272 healthy hospital workers without a history of vascular disease were selected as a control group. The MTHFR-genotype was determined by PCR and gel-electrophoresis. A methionine-loading test was performed on 245 patients, and, in addition to homocysteine, levels of folate and vitamin B12 were measured. We found a strong correlation between MTHFR genotype and plasma homocysteine levels both before and after methionine loading. In addition, the MTHFR genotype seems important for the inverse relationship between homocysteine and folate and vitamin B12 levels. Lastly, the MTHFR genotype distribution was not different between patient and control groups. MTHFR genotype is a strong determinant of plasma homocysteine levels. Moreover, the plasma level of folate, which by itself influences homocysteine levels, is also dependent on the MTHFR genotype. In Val/Val genotypes, low levels of both folate and B12 lead to a relatively large increase in homocysteine levels. Nevertheless, the MTHFR genotype does not increase the risk for premature coronary artery disease.

Authors+Show Affiliations

Laboratory for Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands. B.J.Verhoeff@amc.uva.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9863549

Citation

Verhoeff, B J., et al. "The Effect of a Common Methylenetetrahydrofolate Reductase Mutation On Levels of Homocysteine, Folate, Vitamin B12 and On the Risk of Premature Atherosclerosis." Atherosclerosis, vol. 141, no. 1, 1998, pp. 161-6.
Verhoeff BJ, Trip MD, Prins MH, et al. The effect of a common methylenetetrahydrofolate reductase mutation on levels of homocysteine, folate, vitamin B12 and on the risk of premature atherosclerosis. Atherosclerosis. 1998;141(1):161-6.
Verhoeff, B. J., Trip, M. D., Prins, M. H., Kastelein, J. J., & Reitsma, P. H. (1998). The effect of a common methylenetetrahydrofolate reductase mutation on levels of homocysteine, folate, vitamin B12 and on the risk of premature atherosclerosis. Atherosclerosis, 141(1), pp. 161-6.
Verhoeff BJ, et al. The Effect of a Common Methylenetetrahydrofolate Reductase Mutation On Levels of Homocysteine, Folate, Vitamin B12 and On the Risk of Premature Atherosclerosis. Atherosclerosis. 1998;141(1):161-6. PubMed PMID: 9863549.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of a common methylenetetrahydrofolate reductase mutation on levels of homocysteine, folate, vitamin B12 and on the risk of premature atherosclerosis. AU - Verhoeff,B J, AU - Trip,M D, AU - Prins,M H, AU - Kastelein,J J, AU - Reitsma,P H, PY - 1998/12/24/pubmed PY - 1998/12/24/medline PY - 1998/12/24/entrez SP - 161 EP - 6 JF - Atherosclerosis JO - Atherosclerosis VL - 141 IS - 1 N2 - An increased total plasma homocysteine level is an established risk factor for atherosclerotic vascular disease. The plasma level of homocysteine is influenced by both environmental and genetic factors. An important genetic determinant of plasma homocysteine is a common amino acid dimorphism (Ala222Val) in the methylenetetrahydrofolate reductase (MTHFR) gene. Individuals homozygous for the Val allele have significantly higher homocysteine levels than those with an Ala/Val or Ala/Ala genotype. Moreover, the Val/Val genotype has been claimed to be a strong genetic risk factor for atherosclerosis. The aim of the present study is: (1) to determine the risk associated with the MTHFR dimorphism by comparing the genotype distribution in patients with premature atherosclerosis with that in a group of healthy controls; and (2) to investigate the relationship between the MTHFR genotype and parameters of homocysteine metabolism. The patient group consisted of 257 consecutive referred individuals with angiographically proven premature (<50 years of age) arterial disease (coronary, and/or peripheral vascular disease). A total of 272 healthy hospital workers without a history of vascular disease were selected as a control group. The MTHFR-genotype was determined by PCR and gel-electrophoresis. A methionine-loading test was performed on 245 patients, and, in addition to homocysteine, levels of folate and vitamin B12 were measured. We found a strong correlation between MTHFR genotype and plasma homocysteine levels both before and after methionine loading. In addition, the MTHFR genotype seems important for the inverse relationship between homocysteine and folate and vitamin B12 levels. Lastly, the MTHFR genotype distribution was not different between patient and control groups. MTHFR genotype is a strong determinant of plasma homocysteine levels. Moreover, the plasma level of folate, which by itself influences homocysteine levels, is also dependent on the MTHFR genotype. In Val/Val genotypes, low levels of both folate and B12 lead to a relatively large increase in homocysteine levels. Nevertheless, the MTHFR genotype does not increase the risk for premature coronary artery disease. SN - 0021-9150 UR - https://www.unboundmedicine.com/medline/citation/9863549/The_effect_of_a_common_methylenetetrahydrofolate_reductase_mutation_on_levels_of_homocysteine_folate_vitamin_B12_and_on_the_risk_of_premature_atherosclerosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9150(98)00156-7 DB - PRIME DP - Unbound Medicine ER -