Myocardial infarction in young women in relation to plasma total homocysteine, folate, and a common variant in the methylenetetrahydrofolate reductase gene

Stephen M. Schwartz, David S. Siscovick, M. Rene Malinow, Frits R. Rosendaal, R. Kevin Beverly, David L. Hess, Bruce M. Psaty, W. T. Longstreth, Thomas D. Koepsell, T. E. Raghunathan, Pieter H. Reitsma

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    Abstract

    Background: In a population-based study, we examined the relationship between the risk of myocardial infarction (MI) among young women and plasma total homocysteine (tHCY), folate, vitamin B12, and a common cytosine (C) to thymine (T) polymorphism in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR). Methods and Results: In-person interviews and nonfasting blood samples were obtained from 79 women <45 years old diagnosed with MI and 386 demographically similar control subjects living in western Washington state between 1991 and 1995. Compared with control subjects, case patients had higher mean tHCY concentrations (13.4±5.2 versus 11.1±4.4 μmol/L, P=.0004) and lower mean folate concentrations (12.4±13.4 versus 16.1±12.2 nmol/L, P=.018). There was no difference in vitamin B12 concentrations between case patients and control subjects (346.8±188.4 versus 349.7±132.4 pmol/L, P=.90). After adjusting for cardiovascular risk factors, we found that women with tHCY ≤15.6 μmol/L were at approximately twice the risk of MI as women with tHCY <10.0 μmol/L (OR, 2.3; 95% CI, 0.94 to 5.64). Women with folate ≤8.39 nmol/L had an ≃50% lower risk of MI than women with folate <5.27 nmol/L (OR, 0.54; 95% CI, 0.23 to 1.28). There was no association with vitamin B12 concentration. Among control subjects, 12.7% were homozygous for the MTHFR T677 allele, and these women had higher plasma tHCY and lower plasma folate than women with other genotypes. Ten percent of case patients were homozygous for the T677 allele, and there was no association of homozygosity for T677 with MI risk (OR, 0.90; 95% CI, 0.31 to 2.29). Conclusions: These data support the hypothesis that elevated plasma tHCY and low plasma folate are risk factors for MI among young women. Although homozygosity for MTHFR T677 is related to increased plasma tHCY and low plasma folate, this genetic characteristic is not a risk factor for MI in this population.

    Original languageEnglish (US)
    Pages (from-to)412-417
    Number of pages6
    JournalCirculation
    Volume96
    Issue number2
    DOIs
    StatePublished - Jul 15 1997

    Keywords

    • Folate
    • Genetics
    • Homocysteine
    • Myocardial infarction
    • Women

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine
    • Physiology (medical)

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    Schwartz, S. M., Siscovick, D. S., Malinow, M. R., Rosendaal, F. R., Beverly, R. K., Hess, D. L., Psaty, B. M., Longstreth, W. T., Koepsell, T. D., Raghunathan, T. E., & Reitsma, P. H. (1997). Myocardial infarction in young women in relation to plasma total homocysteine, folate, and a common variant in the methylenetetrahydrofolate reductase gene. Circulation, 96(2), 412-417. https://doi.org/10.1161/01.CIR.96.2.412