Genetic Polymorphisms as Biomarkers of Neuroinflammation Pathway in Neurodegenerative Sclerosis: A Systematic Review and Meta-Analysis

Abstract

Abstract Degenerative sclerosis, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) are progressive diseases affecting neuronal cells, impairing muscle tone and mobility. Both pathologies have a multifactorial etiology. However, inflammation plays a significant role in neuron injury, and the genetic background can influence its susceptibility and progression. In this context, we perform a systematic review and meta-analysis aiming to identify the genetic polymorphisms that directly activate inflammatory pathways to neurodegeneration. Through research in EMBASE, SCOPUS, Web of Science, Pubmed/NCBI, and virtual health library (BVS) databases, on observational studies that addressed polymorphisms and direct neuroinflammation in ALS and/or MS presenting a statistically significant association. Studies on non-humans, non-observational reports, studies reporting indirect activation of inflammatory pathways, protective genetic association, or susceptibility only to the diseases’ progression were excluded. The methodological quality of the individual studies was assessed by Joanna Briggs Critical Appraisal Tools. Forty-two studies were included by a qualitative synthesis in this systematic review, and five polymorphisms were evaluated in the meta-analysis. For MS, the gene superfamily of interleukins was frequently reported, while VEGF-A was the major cytokine associated with ALS. In the meta-analysis, the SNPs rs2069762 in IL2, rs3212227 in IL12Β, rs1946518 in IL18, and rs3918242 in MMP9 were associated with MS susceptibility. No association was found for rs1800750 in the TNF-α gene. Despite limitations, such as the small sample size, this review highlights key genes and polymorphisms in neuroinflammatory pathways, offering insights for developing a genetic panel targeting ALS and MS susceptibility.