Abstract
With a feature of complex pathogenic mechanisms, migraine is a well-known common neurovascular disorder. Multiple genes are responsible for hindering the susceptibility of pain threshold one of which is the eNOS gene and its variants. Multiple independent observational studies with case–control design produced conflicting findings, which can be attributed to a variety of factors including varying sample sizes, demographic stratification, technique application, etc. Therefore, in the present study we aimed to find out the precise risk between the selected variant of eNOS and the risk of migraine and its clinical subtypes using a meta-analysis approach. To find the association between the risk variants of the eNOS gene and migraine, a PRISMA-based systematic literature review strategy was utilized to search via online resources including PubMed and Google Scholar. Using several genetic models, odds ratios with 95% confidence intervals were computed to pool the data. To access heterogeneity, Cochran's Q Test and I2 statistics were utilized, while Begg's and Egger's tests were used to determine publication bias. A p-value of 0.05 or below was deemed statistically significant for all two-sided tests. The present meta-analysis was able to find out the significant protective association between rs743506 and migraine after using dominant (OR: 0.66, CI [0.49–0.86]), over-dominant (OR: 0.56, CI [0.42–0.75]), codominant model (OR: 0.58, CI[0.43–0.77]). Only significant risk association was found between rs1799983, rs3918226, and risk of migraine with aura after utilizing recessive and codominant models i.e., HR vs HW and HR vs HT. The present meta-analysis showed that rs743506 showed a protective association in comparison to rs1799983, rs3918226 which showed significant risk in the MA group. Also, TSA showed non-significant results and therefore, in conclusion, more studies are required to establish risk.
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All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.
Abbreviations
- ICHD-3 :
-
International Classification of Headache Disorder 3rd edition
- MA :
-
Migraine Aura
- MWA :
-
Migraine without Aura
- eNOS :
-
Endothelial Nitric Oxide Synthase
- ICHD-3 :
-
International Classification of Headache Disorders
- NCBI :
-
National Centre for Biotechnology Information
- MEDLINE :
-
Medical Literature Analysis and Retrieval System Online
- PRISMA :
-
Preferred Reporting Items for Systematics Reviews and Meta-Analysis
- IHS :
-
International Headache Society
- HWE :
-
Hardy-Weinberg Equilibrium
- OR :
-
Odds Ratio
- CI :
-
Confidence Interval
- I 2 :
-
I Square
- GAS :
-
Gene Association Study
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Acknowledgements
The authors are highly thankful to the Institute of Human Genetics, University of Jammu, and Department of Human Genetics (Sri Pratap College, Srinagar, Cluster University Srinagar) for support in the present study.
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Detail of the author’s contribution, according to the CRediT (Contributor Roles Taxonomy) System: PK & AS conceptualized the study and provided supervision, M.B, A.C.P &KSdownloaded and filtered the data, AS, KSconducted all the statistical analysis, and interpretation. A.Sdrafted the manuscript, pictures, and tables editing, HK & PK edited the manuscript and PK finalized the manuscript. All authors provided critical feedback on drafts and approved the final manuscript.
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Sudershan, A., Bhagat, M., Singh, K. et al. A Comprehensive Investigation of Risk Association Between the -786 T > C, + 884 G > A, VNTR, rs743506, rs3918226 of eNOS and Susceptibility of Migraine: A Updated Meta-Analysis Utilizing Trial Sequential Analysis. J Mol Neurosci 73, 956–975 (2023). https://doi.org/10.1007/s12031-023-02167-2
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DOI: https://doi.org/10.1007/s12031-023-02167-2