Evidence on the causal link between homocysteine and hypertension from a meta-analysis of 40 173 individuals implementing Mendelian randomization.
Level 3 - non-randomized controlled study
Meta-analysis of observational genetic association studies using Mendelian randomization
PubMed 31769183 · doi:10.1111/jch.13737
What was done
A Mendelian randomization meta-analysis was performed using the MTHFR C677T polymorphism as an instrumental variable to examine whether elevated homocysteine concentration causes hypertension. The authors pooled data from eligible studies comprising 14,378 hypertension cases and 25,795 controls (40,173 total individuals) to assess relationships between MTHFR C677T, homocysteine concentrations, and hypertension risk.
What was found
The MTHFR C677T polymorphism was associated with hypertension risk (T vs C: OR = 1.27, 95% CI: 1.17-1.37; TT vs CC: OR = 1.53, 95% CI: 1.30-1.79). Among hypertensive subjects, individuals with the TT genotype had 7.74 μmol/L higher homocysteine (95% CI: 5.25-10.23) than those with the CC genotype. Overall, hypertensive subjects had 0.69 μmol/L higher homocysteine (95% CI: 0.50-0.87) than controls. Mendelian randomization estimated a causal OR for hypertension of 1.32 per 5 μmol/L increase in homocysteine.
Why it matters
This study provides genetic instrumental-variable evidence supporting a potential causal role for elevated homocysteine in hypertension pathogenesis.
Limits
The abstract does not report the number of included studies, demographic or ancestral characteristics of participants, or assessments of between-study heterogeneity. Mendelian randomization using a single gene variant (MTHFR C677T) is susceptible to potential pleiotropy or gene-diet interactions such as folate status, which were not reported.
Cited by
- supports Elevated homocysteine is a cause of high blood pressure.