A Comprehensive Investigation into the Association Between Mthfr C677t, A1298c, and Ace I/D Variants and Risk of Migraine: an Updated Meta-Analysis of Genetic Association Studies with Trial Sequential Analysis and Meta-Regression

Abstract

Many homeostatic genes are thought to play a role in the susceptibility to migraine, making it a highly complex neurovascular disease. In this meta-analysis, our primary objective was to evaluate whether or not MTHFR variants (such as C677T and A1289C) and ACE I/D were associated with an increased risk of migraine. Using a PRISMA-based systematic literature-review guideline, internet sources such as PubMed and Google Scholar were searched to identify the genes of interest and migraine risk. To pool the data, odds ratios with 95% confidence intervals were calculated utilizing different genetic models. Cochran’s Q Test and I² statistics were used to access heterogeneity, while Begg’s and Egger’s tests were used to identify publication bias. All tests were two-sided, and a p-value of < 0.05 was regarded as statistically significant. The present meta-analysis observed that the C677T variant is significantly associated with the increased risk of migraine (allele model: OR:1.19, CI [1.07–1.33], I² = 78%) and its clinical subtype i.e., MA (allele model: OR: 1.26, CI [1.09–1.45], I² = 80%) in the overall population. Concerning the ACE- I/D, it significantly increased the risk of overall migraine and both clinical subtypes after utilizing the dominant genetic models (OR: 1.14, CI [1.01–1.29], I²% = 32). Concerning the MTHFR A1289C, only the codominant model (HR vs HT) and recessive model significantly increased the risk of overall migraine. Therefore, the findings of the present meta-analysis showed that MTHFR-C677T is an important risk factor for migraine and its clinical subtype.

Graphical Abstract

Full text

Vol:.(1234567890)
Journal of Molecular Neuroscience (2023) 73:884–911
https://doi.org/10.1007/s12031-023-02164-5
1 3
A Comprehensive Investigation intotheAssociation Between Mthfr
C677t, A1298c, andAce I/D Variants andRisk ofMigraine: anUpdated
Meta‑Analysis ofGenetic Association Studies withTrial Sequential
Analysis andMeta‑Regression
AmritSudershan1,2· AgarChanderPushap3· HardeepKumar4· ParvinderKumar1,5
Received: 5 September 2023 / Accepted: 29 September 2023 / Published online: 16 October 2023
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023
Abstract
Many homeostatic genes are thought to play a role in the susceptibility to migraine, making it a highly complex neuro-
vascular disease. In this meta-analysis, our primary objective was to evaluate whether or not MTHFR variants (such as
C677T and A1289C) and ACE I/D were associated with an increased risk of migraine. Using a PRISMA-based systematic
literature-review guideline, internet sources such as PubMed and Google Scholar were searched to identify the genes of
interest and migraine risk. To pool the data, odds ratios with 95% confidence intervals were calculated utilizing different
genetic models. Cochran’s Q Test and I2 statistics were used to access heterogeneity, while Begg’s and Egger’s tests were
used to identify publication bias. All tests were two-sided, and a p-value of < 0.05 was regarded as statistically significant.
The present meta-analysis observed that the C677T variant is significantly associated with the increased risk of migraine
(allele model: OR:1.19, CI [1.07–1.33], I2 = 78%) and its clinical subtype i.e., MA (allele model: OR: 1.26, CI [1.09–1.45],
I2 = 80%) in the overall population. Concerning the ACE- I/D, it significantly increased the risk of overall migraine and both
clinical subtypes after utilizing the dominant genetic models (OR: 1.14, CI [1.01–1.29], I2% = 32). Concerning t he MTHFR
A1289C, only the codominant model (HR vs HT) and recessive model significantly increased the risk of overall migraine.
Therefore, the findings of the present meta-analysis showed that MTHFR-C677T is an important risk factor for migraine
and its clinical subtype.
Keywords Migraine· MTHFR· ACE· C677T· A1289C· ACE I/D
Introduction
Migraine is generally recognized as the third most debili-
tating and prevalent condition and is classified as a neuro-
vascular disorder (Steiner etal. 2020; Sudershan etal. 2022).
Depending on whether or not an aura feature is present dur-
ing an attack, the disease is classified as migraine with aura
(MA) or migraine without aura (MWA) by the International
Classification of Headache Disorder-III (ICHD-3.org/1-
migraine/). Comprehending the susceptibility to diseases is
an important factor, and in the case of migraine, it is defined
by various risk variables that are roughly classified as envi-
ronmental and genetic risk factors, with the former being
responsible for hindering the sensitivity threshold of pain
established by the latter, i.e., genetic risk factors (Sudershan
etal. 2022). The most recent and updated meta-analysis of
the genome-wide association study (GWAS) data has shown
* Parvinder Kumar
drparvinderkumar@jammuuniversity.ac.in;
parvinderkb2003@gmail.com
1 Institute ofHuman Genetics, University ofJammu, Jammu
and Kashmir 180006, Gujarbasti,Jammu, India
2 Department ofHuman Genetics, Sri Pratap College,
Cluster University ofSrinagar, Jammu and Kashmir,
Kashmir190001, India
3 Department ofEducation, Dakshina Bharat Hindi Prachar
Sabha, Madras600017, India
4 Department ofNeurology, Super Specialty Hospital, Jammu
and Kashmir 180006, Jammu, India
5 Department ofZoology, University ofJammu, Jammu and
Kashmir 180006, Gujarbasti,Jammu, India
Content courtesy of Springer Nature, terms of use apply. Rights reserved.