Abstract

BackgroundElevated total plasma homocysteine (tHcy) in humans is associated with cardiovascular disease but prevention trials have failed to confirm causality. Reported reasons for this association have been that homocysteine and its major genetic determinant methylenetetrahydrofolate reductase (MTHFR) may have an effect on HDL and Apolipoprotein (Apo) A1 levels. We wanted to study if tHcy and its major determinants were correlated with Apo A1 levels in a large population without folate fortification.MethodsThis study was a prospective incident nested case-referent study within the Northern Sweden Health and Disease Study Cohort (NSHDSC), including 545 cases with first myocardial infarction and 1054 matched referents, median age at inclusion was 59 years. Univariate and multiple regression analyzes was used to study the associations between apolipoproteins Apo A1 and B, tHcy, folate and vitamin B12 in plasma as well as MTHFR polymorphisms 677C>T and 1298A>C.ResultsApo A1 and Apo B were strongly associated with the risk of a first myocardial infarction. tHcy was not associated with Apo A1 levels. Instead, folate had an independent positive association with Apo A1 levels in univariate and multiple regression models. The associations were seen in all men and women, among referents but not among cases. MTHFR polymorphisms had no clear effect on Apo A1 levels.ConclusionsAnalyzing over 1500 subjects we found an independent positive association between plasma folate (major dietary determinant of tHcy) and Apo A1 levels among those who later did not develop a first myocardial infarction. No association was seen between tHcy and Apo A1.

Highlights

  • Elevated total plasma homocysteine in humans is associated with cardiovascular disease but prevention trials have failed to confirm causality

  • The aim of this study was to investigate if total plasma homocysteine (tHcy) and its major determinants folate, vitamin B12 and methylenetetrahydrofolate reductase (MTHFR) polymorphism are correlated with Apo Apolipoprotein A1 (A1) levels in over 1500 subjects, without folate fortification, including both men and women and to see if this correlation was present among those who did and did not develop a first myocardial infarction

  • We have previously reported that homocysteine levels were positively associated and folate concentrations in plasma were inversely associated with first myocardial infarction in this cohort [1]

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Summary

Introduction

Elevated total plasma homocysteine (tHcy) in humans is associated with cardiovascular disease but prevention trials have failed to confirm causality. Reported reasons for this association have been that homocysteine and its major genetic determinant methylenetetrahydrofolate reductase (MTHFR) may have an effect on HDL and Apolipoprotein (Apo) A1 levels. Cell studies have shown that mRNA levels of Apo A1 are affected by homocysteine and MTHFR-polymorphism [27] This would suggest that hyperhomocysteinemia may be associated with an increased risk of atherosclerosis due to decreased expression of Apo A1 [16,23,27,28,29]. Some studies have failed to demonstrate an association between Apo A1 and / or HDL with tHcy [30,31,32,33] and MTHFR polymorphisms [22,31]

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