RANK Gene Polymorphism Is Associated With Incidence Of Stress Fractures In Japanese Female Endurance Athletes

Abstract

In female endurance athletes, stress fractures are induced by repeated mechanical loading and various factors are involved in the development of stress fracture. The receptor activator of nuclear factor-kappa B (RANK) and its ligand (RANKL) are a member of the tumour necrosis factor superfamily and stimulate mature osteoclasts to resorb bone. However, effect of development of stress fractures on RANK and RANKL gene polymorphisms remains unclear in Japanese female endurance athletes. PURPOSE: This study aimed to clarify whether single nucleotide polymorphisms (SNPs) within the RANK and RANKL genes were associated with the incidence of stress fracture in Japanese female endurance athletes. METHODS: Twenty-four Japanese elite female long-distance runners (20±1 years, 160±4 cm, 48±4 kg, 15±4 %fat, Mean±SD) participated in a cross-sectional study. All subjects were investigated the onset number of stress fractures and medial tibial stress syndrome in the student period of the university from high school by using a questionnaire. SNPs of rs3018362 in RANK gene and rs1021188 in RANKL gene were determined by real-time PCR with Taqman probe. RESULTS: The onset number of stress fractures in the student period of the university from high school was significantly higher in the AA genotype of rs3018362 in RANK gene compared with the GA and GG genotype individuals (P<0.05). Moreover, the onset number of stress fractures and medial tibial stress syndrome in a student period of a university was significantly higher in the AA genotype of rs3018362 in RANK gene compared with other genotype individuals (each P<0.05). However, the rs1021188 in RANKL gene polymorphism had no impact on differences of the onset number of stress fractures and medial tibial stress syndrome. CONCLUSION: These results suggest the association between SNPs of rs3018362 in the RANK gene polymorphism and the incidence of stress fracture in Japanese female endurance athletes. Supported by Grants-in-Aid for Scientific Research (#26282199 and 16K13059, M. Iemitsu).