Lack of association of VEGF-A polymorphisms and susceptibility to amyotrophic lateral sclerosis and multiple sclerosis: A systematic review and meta-analysis

Amyotrophic lateral sclerosis (ALS) and multiple sclerosis ( MS) are degenerative scleroses with unclear etiology. Vascular endothelial growth factor A (VEGF-A) is a growth factor that plays multiple roles in the central nervous system. Previous studies indicated a potential association between polymorphisms in this gene and the susceptibility of ALS and MS; however, the results have been inconclusive. Here, we conducted a systematic review and meta- analysis to elucidate the relationship between polymorphisms in the VEGF-A gene and these degenerative scleroses. We searched for observational studies in PubMed, Web of Science, EMBASE, Virtual Health Library (BVS) and SCOPUS, without temporal and language restrictions and 12 studies were included in the systematic review. Six polymorphisms were identified: C-1558T, A-1190G, G-1154A (rs1570360), C-2578A (rs699947), C-634G (rs2010963), and C936T (rs3025039). After a systematic literature search, a pooled odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association of C- 2578A, G-1154A, and G-634C polymorphisms and ALS. Due to the small number of articles found in this review for MS, it was not possible to perform a meta-analysis for this disease. The meta-analysis for ALS included 1441 patients and 1978 controls for C-2578A, and 1134 patients and 1629 controls for G-1154A and G-634C polymorphisms. No SNP was significantly associated with risk for ALS. We conclude that polymorphisms in the VEGF-A gene may not be a major risk factor for the development of ALS and MS; However, associated with specific factors, such as sex or haplotype combinations, they may become a strong susceptibility factor. Although we found a lack of association in most VEGF-A polymorphisms and the susceptibility for developing ALS and MS, this review provides a comprehensive understanding for the potential role of this gene in degenerative sclerosis.

Automated summary

This study conducted a systematic review and meta-analysis to investigate the association between polymorphisms in the VEGF-A gene and ALS and MS. The results suggest that VEGF-A gene polymorphisms may not be major risk factors for ALS and MS development, but they may become strong susceptibility factors when associated with specific factors such as sex or haplotype combinations.