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Is there a causal role for homocysteine concentration in blood pressure? A Mendelian randomization study

Maria C Borges1, Fernando P Hartwig2, Isabel O Oliveira3

  • 1Postgraduate Program in Epidemiology and carolina.borges.mcb@gmail.com.

The American Journal of Clinical Nutrition
|December 18, 2015
PubMed

Insights

This study investigated if homocysteine causally affects blood pressure. Findings suggest homocysteine does not have a causal role in systolic blood pressure, and its role in diastolic blood pressure is inconsistent.

Area of Science:

  • Cardiovascular Health
  • Nutritional Biochemistry
  • Genetic Epidemiology

Background:

  • Elevated homocysteine levels are linked to increased blood pressure, but a causal relationship is debated.
  • Effective and safe interventions exist to lower homocysteine, making this understanding clinically relevant.

Purpose of the Study:

  • To determine the causal influence of homocysteine on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults.
  • Utilize Mendelian randomization (MR) to assess causality, differentiating between marker and cause.

Main Methods:

  • Employed Mendelian randomization (MR) using data from the 1982 Pelotas Birth Cohort and the International Consortium for Blood Pressure (ICBP).
  • Utilized the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) and other homocysteine-associated SNPs as genetic instruments.
  • Assessed associations using ordinary least-squares (OLS) and 2-stage least-squares (2SLS) regression.

Main Results:

  • OLS regression showed a positive association between homocysteine and both SBP and DBP.
  • MR analysis in the Pelotas cohort indicated no significant causal effect on SBP and a non-significant trend for DBP.
  • MR analysis in ICBP data revealed no association with SBP but a positive association with DBP, though inconsistent across SNPs.

Conclusions:

  • The study's findings do not support a causal role for homocysteine in blood pressure, particularly systolic blood pressure.
  • The evidence does not corroborate the hypothesis that homocysteine is a causal factor in hypertension.
Abstract

Keywords:
Mendelian randomizationblood pressurecohort studieshomocysteinemolecular epidemiology

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