In a study evaluating the impacts of 5 growth factors on MS, fibroblast growth factor 23 was identified as increasing the risk of the onset and progression of multiple sclerosis (MS) in patients.
A recent meta-analysis confirmed a causal relationship between fibroblast growth factor (FGF) 23 and the risk of multiple sclerosis (MS), suggesting that certain growth factors play a critical role in the risk of the disease.
The study, published in Frontiers in immunology, took advantage of a large sample of genetic data from multiple sources to determine if there is a causal relationship between MS and growth factors, including FGF23 as well as growth differentiation factor 15 (GDF15) , insulin growth factor 1 (IGF1), insulin-like growth factor-binding proteins 3 (IGFBP3) and vascular endothelial growth factor (VEGF).
MS affects approximately 2.8 million people worldwide and is diagnosed in 2.1 out of 100,000 people each year. The etiology and mechanisms of the disease are not fully understood and further studies are needed to improve the understanding of its nasogenesis.
Growth factors regulate cytokines that aid in cell proliferation, differentiation, and activation. Previous research has suggested that growth factors act as risk factors for MS and play an important role in the initiation and progression of the disease.
Among the 5 growth factors included in the analysis, FGF23 is known to regulate various biological functions and is an essential player in the metabolism of vitamin D. GDF15 regulates inflammation and apoptosis in various diseases and is known to be positively correlated with MS disability scores. VEGF contributes to the breakdown of the blood-brain barrier (BBB) ââand is detected in the serum and central nervous tissue of patients with MS.
IGF1 protects neuron and glial cell survival, stimulates myelin regeneration, attenuates BBB damage, and relieves immune-mediated inflammation. IGF1 is also associated with susceptibility to MS. IGF1 is regulated by IGFBP3, which is the most abundant IGFBP in human serum and can directly inhibit cell growth. Reduced levels of IGFBP3 and reduced bioavailability of IGF1 are frequently reported in the serum of patients with MS.
Researchers used data from genome-wide association studies to perform a 2-sample Mendelian Randomization (RM) analysis to understand the potential causal roles these growth factors might play in MS risk. . Genetic instruments and meta-analyzes have been used to examine the roles of growth factors in patients of European descent:
- FGF23: 7 studies involving 16,624 patients (mean age range: 36.4 – 78.0 years; 54.5% women)
- GDF15: 4 community cohort of 5,440 patients (mean age 62.0 years; 53.0% women)
- IGF1: 451,993 patients (mean age, 56.5 years; 54.0% women)
- IGFBP3: 13 studies including 18,995 patients (57.6% women)
- VEGF: meta-analysis including 16,112 patients (mean age, 54.8 years; 54.0% women)
Primary magnetic resonance analysis showed that circulating levels of FGF23 were inversely associated with the risk of MS, with an odds ratio (OR) of 0.63 (95% CI: 0.49-0.82; P = .00047). The weighted median estimators identified that FGF23 was also associated with a lower risk of MS (OR, 0.67; 95% CI: 0.51-0.87; P = 0.0031).
âOur result also implied a potential therapeutic role of FGF23 for the treatment of MSâ¦. Further clinical trials are needed to explore the potential therapeutic effects of FGF23 in patients with MS,â the researchers wrote.
FGF23 was the only growth factor examined in the analysis that was found to be associated with the risk of MS. Genetically predicted concentrations of GDF15 (OR, 0.96; 95% CI, 0.90-1.04; P = 0.33), IGF1 (OR, 1.06; 95% CI, 0.94-1.19; P = 0.35), IGFBP3 (OR, 1.01; 95% CI, 0.92-1.11; P = 0.77) and VEGF (OR, 0.99; 95% CI, 0.94-1.06; P = 0.84) demonstrated no causal relationship with MS.
The study had several limitations, including the fact that magnetic resonance analyzes do not replace randomized controlled trials and are subject to the presence of linkage imbalance, cryptic relatedness, genetic heterogeneity, pleiotropy, channeling, or covariate fit. Additionally, the genetic data used in the analysis was collected only from European populations, suggesting that generalization to other populations is limited. Possible differences by sex were also not examined.
Lu H, Wu PF, Ma DL, Zhang W, Sun M. Growth factors and their roles in multiple sclerosis risk. Immunol before. 2021; 12: 768682. doi: 10.3389 / fimmu.2021.768682