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Homozygosity for the C677-->T mutation of 5,10-methylenetetrahydrofolate reductase and total plasma homocyst(e) ine are not associated with greater than normal risk of a first myocardial infarction in northern Sweden
Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
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2001 (English)In: Coronary Artery Disease, ISSN 0954-6928, Vol. 12, no 2, 85-90 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Results of several case-control studies have shown elevated total plasma homocyst(e)ine (TPH) and homozygosity for the point mutation C677-->T in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) to be associated with a greater than normal risk of atherosclerotic vascular disease. However, there have been few epidemiologic studies and the interpretation of the results is not clear-cut. OBJECTIVE: To elucidate whether homozygosity for the point mutation C677-->T in the gene for MTHFR, and TPH are risk factors for a first myocardial infarction. DESIGN: A prospective nested case-control study in Northern Sweden. METHODS: Among more than 36000 persons screened, 78 cases satisfied the inclusion criterion of having developed, after sampling, a first myocardial infarction. For each case, two controls matched for sex and age were randomly selected. RESULTS: We found no statistically significant difference among the prevalences of the three possible MTHFR genotypes -/- (no mutation), +/+ (both alleles have the mutation), and +/- among cases and controls in univariate conditional logistic regression analysis. Mean levels of TPH in patients and controls were 12.2+/-4.9 and 12.2+/-3.5 micromol/l (means +/- SD), respectively (NS). CONCLUSIONS: In this study neither homozygosity for the point mutation C677-->T in the gene for MTHFR nor TPH was related to a greater than normal risk of a first myocardial infarction for members of the population of northern Sweden. Further research is needed in order to show whether TPH is an independent risk factor for a first myocardial infarction.

Place, publisher, year, edition, pages
2001. Vol. 12, no 2, 85-90 p.
Identifiers
URN: urn:nbn:se:umu:diva-4720PubMedID: 11281306OAI: oai:DiVA.org:umu-4720DiVA: diva2:143940
Available from: 2005-09-29 Created: 2005-09-29Bibliographically approved
In thesis
1. Risk markers for a first myocardial infarction
Open this publication in new window or tab >>Risk markers for a first myocardial infarction
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The development of a first myocardial infarction is associated with a large number of contributing factors. Age, male sex, hypertension, smoking, diabetes, body mass index and hypercholesterolemia are considered as established risk factors.

The primary aim of the present dissertation was to evaluate whether specific biomarkers could improve the prediction of subjects at risk for a first myocardial infarction when considered in addition to established cardiovascular risk factors. The biomarkers investigated include: tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), thrombomodulin (TM), von Willebrand factor (VWF), dehydroepiandrosterone sulfate (DHEAS), lipoprotein (a) (Lp(a)), leptin, apolipoproptein A1 (ApoA1), proinsulin, homocysteine and homozygosity for the 5,10- methylenetetrahydrofolate reductase (MTHFR) C>T genotype. A secondary objective was to determine whether a first myocardial infarction leads to increased plasma homocysteine concentrations and whether the association between homocysteine and myocardial infarction was greater at follow-up compared to baseline.

The study population consisted of 36 405 subjects screened and included in the Västerbotten Intervention Program and the Northern Sweden MONICA cohorts between January 1, 1985 and September 30, 1994. A nested incident case-referent study design was used. Seventy eight cases with a first myocardial infarction were identified, and from the same cohort twice as many sex and age matched referents were randomly selected. Moreover, a follow-up health survey (average 8.5 years between surveys) was conducted with 50 cases and 56 matched referents.

High plasma levels of tPA and PAI-1 mass concentration, VWF, proinsulin, leptin and Lp(a) and low plasma levels of ApoA1 were associated with subsequent development of a first myocardial infarction in univariate conditional logistic regression analysis. For PAI-1 and tPA, this relation was found in both men and women. For tPA, but not for PAI-1 and VWF, this association was independent of established risk factors. In women, high plasma concentrations of TM were associated with significant increases in risk of a first myocardial infarction. No predictive values of DHEAS, homocysteine or for the point mutation C677>T in the gene for MTHFR was found regarding the risk of a first myocardial infarction. The summarised importance of haemostatic and metabolic variables (proinsulin, lipids including Lp(a) and leptin) in predicting first myocardial infarction in men, as well as possible interactions among these variables, were studied. High tPA and Lp(a) and low ApoA1 remained significant risk markers in multivariate analysis independent of established risk factors. There were non-significant synergic interactions between high Lp(a) and leptin and tPA respectively, and between high Lp(a) and low ApoA1.

In the follow-up study plasma homocysteine and plasma creatinine increased significantly, and plasma albumin decreased significantly over time. Conditional univariate logistic regression indicated that high homocysteine at follow-up but not at baseline was associated with first myocardial infarction but the relation disappeared in multivariate analyses including plasma creatinine and plasma albumin. High plasma creatinine remained associated with first myocardial infarction at both baseline and follow-up.

In conclusion, the present results support the hypothesis that biomarkers, in addition to the traditional cardiovascular risk factors, carry predictive information on the risk of developing a first myocardial infarction.

Place, publisher, year, edition, pages
Umeå: Folkhälsa och klinisk medicin, 2005. 107 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 975
Keyword
haemostatis, lipoprotein (a), MTHFR, homocysteine, proinsulin, leptin, apolipoprotein A1, DHEAS, myocardial infarction, risk factors
Identifiers
urn:nbn:se:umu:diva-603 (URN)91-7305-909-9 (ISBN)
Public defence
2005-09-16, sal D, Tandläkarhögskolan, 9tr., Umeå, 09:00 (English)
Opponent
Available from: 2005-09-29 Created: 2005-09-29 Last updated: 2009-11-30Bibliographically approved

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