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Irisin is a myokine that acts on several target organs including brain adipose tissue and bone. The present study was finalized to explore circulating levels of irisin in children and adult PWS patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seventy-eight subjects with PWS, 26 children (15 females, mean age 9.48\u2009\u00b1\u20093.6\u00a0years) and 52 adults (30 females, mean age 30.6\u2009\u00b1\u200910.7) were enrolled. Irisin serum levels were measured in patients and controls. Its levels were related with anthropometric and metabolic parameters, cognitive performance and bone mineral density either in pediatric or adult PWS. Multiple regression analysis was also performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Irisin serum levels in PWS patients did not show different compared with controls. A more in-depth analysis showed that both pediatric and adult PWS with DEL15 displayed significantly reduced irisin levels compared to controls. Otherwise, no differences in irisin concentration were found in UPD15 patients with respect to controls. Our study revealed that in pediatric PWS the 25(OH) vitamin-D levels affected irisin serum concentration. Indeed, patients who were not supplemented with vitamin D showed lower irisin levels than controls and patients performing the supplementation. Multiple regression analysis showed that irisin levels in pediatric and adult PWS were predicted by the genetic background and 25(OH)-vitamin D levels, whereas in a group of 29 adult PWS also by intelligent quotient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We demonstrated the possible role of genetic background and vitamin-D supplementation on irisin serum levels in PWS patients.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s40618-021-01533-4","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T09:04:20Z","timestamp":1614762260000},"page":"2261-2271","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The genetic background and vitamin D supplementation can affect irisin levels in Prader\u2013Willi syndrome"],"prefix":"10.1007","volume":"44","author":[{"given":"M. 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