We assessed the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively.<h4>Results</h4>Endothelin-1 concentrations were significantly higher in SSc patients than in controls (26 studies; standardised mean difference, SMD = 0.98, 95% CI 0.73-1.23, <i>P</i> < .001; moderate certainty of evidence). This evidence concerns the gene EDN1 and systemic sclerosis.