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Determinants of fasting and post-methionine homocysteine levels in families predisposed to hyperhomocysteinemia and premature vascular disease.

Abstract

Elevated plasma total homocysteine (tHcy) levels, either measured in the fasting state or after oral methionine loading, are associated with an increased risk of atherothrombotic disease. Fasting and post-methionine hyperhomocysteinemia (HHC) overlap to a limited extent; both can occur as familial traits. We investigated determinants of fasting, postmethionine and delta (ie, post-methionine minus fasting levels) tHcy levels in 510 subjects of 192 HHC-prone families including 161 patients with clinical vascular disease and 349 without vascular disease. We focused on tHcy levels in relation to levels of vitamin B12, B6 and folate and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Multivariate linear analyses adjusted for the presence of vascular disease showed that fasting tHcy was significantly related to folate and vitamin B12, and the presence of the MTHFR TT genotype and the T allele, and to age, smoking habits, and serum levels of creatinine. Both post-methionine and delta tHcy levels were related to serum folate levels, and the presence of the MTHFR TT genotype and the T allele, and to postmenopausal status, and body mass index. An interaction was found between MTHFR TT genotype and serum folate levels for both fasting and post-methionine tHcy, ie, for a given decrease in serum folate, homocysteine levels increased more in subjects with the TT genotype than in those with the CC genotype. Fasting, post-methionine and delta tHcy were higher in patients with vascular disease than in their healthy siblings, but these levels were less dependent on serum folate levels (P<0.05), whereas the effect of MTHFR genotype was stronger (P=0.01). This study found evidence that post-methionine and delta tHcy levels are not only influenced by factors affecting homocysteine transsulfuration but also by factors that affect remethylation. The explained variances of fasting, post-methionine and delta tHcy were 49%, 62%, and 78%, respectively. We also found evidence, in patients with premature vascular disease but not in their healthy siblings, for a factor that increases tHcy levels but weakens the normal inverse relation between folate and tHcy and amplifies the effect of the MTHFR genotype.

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  • Authors+Show Affiliations

    ,

    Institute for Cardiovascular Research, Department of Surgery, Academisch Ziekenhuis, Vrije Universiteit, Amsterdam, The Netherlands.

    , , , , , ,

    Source

    MeSH

    Adult
    Age Factors
    Amino Acid Substitution
    Arteriosclerosis
    Body Mass Index
    Comorbidity
    Fasting
    Female
    Folic Acid
    Genetic Predisposition to Disease
    Genotype
    Homocysteine
    Humans
    Hyperhomocysteinemia
    Hypertension
    Lipids
    Male
    Menopause
    Methionine
    Methylenetetrahydrofolate Reductase (NADPH2)
    Middle Aged
    Oxidoreductases Acting on CH-NH Group Donors
    Polymorphism, Genetic
    Pyridoxine
    Smoking
    Vitamin B 12

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    10323785

    Citation

    de Jong, S C., et al. "Determinants of Fasting and Post-methionine Homocysteine Levels in Families Predisposed to Hyperhomocysteinemia and Premature Vascular Disease." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 19, no. 5, 1999, pp. 1316-24.
    de Jong SC, Stehouwer CD, van den Berg M, et al. Determinants of fasting and post-methionine homocysteine levels in families predisposed to hyperhomocysteinemia and premature vascular disease. Arterioscler Thromb Vasc Biol. 1999;19(5):1316-24.
    de Jong, S. C., Stehouwer, C. D., van den Berg, M., Kostense, P. J., Alders, D., Jakobs, C., ... Rauwerda, J. A. (1999). Determinants of fasting and post-methionine homocysteine levels in families predisposed to hyperhomocysteinemia and premature vascular disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 19(5), pp. 1316-24.
    de Jong SC, et al. Determinants of Fasting and Post-methionine Homocysteine Levels in Families Predisposed to Hyperhomocysteinemia and Premature Vascular Disease. Arterioscler Thromb Vasc Biol. 1999;19(5):1316-24. PubMed PMID: 10323785.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Determinants of fasting and post-methionine homocysteine levels in families predisposed to hyperhomocysteinemia and premature vascular disease. AU - de Jong,S C, AU - Stehouwer,C D, AU - van den Berg,M, AU - Kostense,P J, AU - Alders,D, AU - Jakobs,C, AU - Pals,G, AU - Rauwerda,J A, PY - 1999/5/14/pubmed PY - 1999/5/14/medline PY - 1999/5/14/entrez SP - 1316 EP - 24 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler. Thromb. Vasc. Biol. VL - 19 IS - 5 N2 - Elevated plasma total homocysteine (tHcy) levels, either measured in the fasting state or after oral methionine loading, are associated with an increased risk of atherothrombotic disease. Fasting and post-methionine hyperhomocysteinemia (HHC) overlap to a limited extent; both can occur as familial traits. We investigated determinants of fasting, postmethionine and delta (ie, post-methionine minus fasting levels) tHcy levels in 510 subjects of 192 HHC-prone families including 161 patients with clinical vascular disease and 349 without vascular disease. We focused on tHcy levels in relation to levels of vitamin B12, B6 and folate and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Multivariate linear analyses adjusted for the presence of vascular disease showed that fasting tHcy was significantly related to folate and vitamin B12, and the presence of the MTHFR TT genotype and the T allele, and to age, smoking habits, and serum levels of creatinine. Both post-methionine and delta tHcy levels were related to serum folate levels, and the presence of the MTHFR TT genotype and the T allele, and to postmenopausal status, and body mass index. An interaction was found between MTHFR TT genotype and serum folate levels for both fasting and post-methionine tHcy, ie, for a given decrease in serum folate, homocysteine levels increased more in subjects with the TT genotype than in those with the CC genotype. Fasting, post-methionine and delta tHcy were higher in patients with vascular disease than in their healthy siblings, but these levels were less dependent on serum folate levels (P<0.05), whereas the effect of MTHFR genotype was stronger (P=0.01). This study found evidence that post-methionine and delta tHcy levels are not only influenced by factors affecting homocysteine transsulfuration but also by factors that affect remethylation. The explained variances of fasting, post-methionine and delta tHcy were 49%, 62%, and 78%, respectively. We also found evidence, in patients with premature vascular disease but not in their healthy siblings, for a factor that increases tHcy levels but weakens the normal inverse relation between folate and tHcy and amplifies the effect of the MTHFR genotype. SN - 1079-5642 UR - https://www.unboundmedicine.com/medline/citation/10323785/Determinants_of_fasting_and_post_methionine_homocysteine_levels_in_families_predisposed_to_hyperhomocysteinemia_and_premature_vascular_disease_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&amp;PAGE=linkout&amp;SEARCH=10323785.ui DB - PRIME DP - Unbound Medicine ER -