RANK/RANKL/OPG pathway: genetic association with history of ischemic stroke in Italian population

Federico Biscetti, S. Giovannini, Silvia Giovannini, G. Straface, Giuseppe Straface, F. Bertucci, Flavio Bertucci, F. Angelini, Flavia Angelini, C. Porreca, Carlo Filippo Porreca, Raffaele Landolfi, Andrea Flex

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12 Citations (Scopus)


OBJECTIVE: RANKL is a member of the TNF superfamily that stimulates chemokine release, monocyte/macrophage matrix migration and matrix metalloproteinase activity and plays an important role in atherosclerosis. In our study, we have evaluated whether RANKL gene polymorphisms are involved in ischemic stroke in Italian subjects. PATIENTS AND METHODS: In a retrospective study we have included 487 patients (242 males, 245 females) with history of ischemic stroke and 543 control subjects without history of ischemic stroke (277 males, 276 females). The rs9533156, and rs2277438 gene polymorphisms of the RANKL gene were analyzed by PCR and restriction fragment length polymorphism. RESULTS: We found that the rs9533156 gene polymorphism of the RANKL gene was significantly (55.0% versus 36.5%, p < 0.0001) and independently (adjusted OR 6.28 [2.34-4.21]) associated with history of ischemic stroke. No statistically significant difference was found between the two groups in our population for the rs2277438 gene polymorphism (p = 439). Furthermore, we have confirmed that rs 3134069, rs 2073617 and rs 2073618 polymorphisms of the OPG gene were significantly and independently associated with cerebrovascular disorders. CONCLUSIONS: The present study identifyes, for the first time, the genetic variant of RANKL as an independent risk factor for ischemic stroke.
Original languageEnglish
Pages (from-to)4574-4580
Number of pages7
JournalEuropean Review for Medical and Pharmacological Sciences
Publication statusPublished - 2016


  • Gene Polymorphism
  • RANK/RANKL/OPG pathway
  • history of ischemic stroke


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