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Low back pain and FokI (rs2228570) polymorphism of vitamin D receptor in athletes.

ABSTRACT: BACKGROUND:Low back pain (LBP) is common in athletes. LBP can be detrimental to athletic performance and health. Factors predisposing to LBP in athletes remain elusive and require further studies. We investigated whether carriage of a specific genotype and/or allele of vitamin D receptor gene (VDR) FokI polymorphism (rs2228570) was a risk factor for LBP in athletes of different sports disciplines. METHODS:This genotype/phenotype association case-control study included 60 Italian athletes (25 females and 35 males; mean age 33.9?±?13.3 years; body-mass-index 23.5?±?3.5 kg/m2) of which 16.7% were swimmers, 11.7% soccer players, 11.7% volleyball players, 10.0% rugby players and other disciplines. VDR-FokI polymorphism was measured by PCR-RFLP in 24 athletes with LBP and 36 athletes without LBP episodes. Absence or presence of the FokI restriction site was denoted "F" and "f", respectively. Other risk factors were evaluated by a questionnaire. RESULTS:The homozygous FF genotype was found in 58.3% (14/24) of athletes with LBP versus 27.8% (10/36) of athletes without LBP, adjusted OR?=?5.78, 95% CI 1.41-23.8, P?=?0.015. The F allele was a 2-fold risk factor to develop LBP, adjusted OR?=?2.55, 95% CI 1.02-6.43, P?=?0.046, while f allele was protective. Exposure to vehicle vibrations ?2 h daily, and family history of lumbar spine pathology were significant risk factors for LBP with OR?=?3.54, and OR?=?9.21, respectively. CONCLUSIONS:This is the first study in which an association between VDR-FokI polymorphism and LBP in athletes was found. Further research is needed to extend our results, and to clarify the biochemical pathways associated with how vitamin D modulates LBP in athletes. The VDR-FokI polymorphism should be considered when developing genetic focused studies of precision medicine on health in athletes.

SUBMITTER: Cauci S

PROVIDER: S-EPMC5294822 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Low back pain and FokI (rs2228570) polymorphism of vitamin D receptor in athletes.

Cauci Sabina S Migliozzi Francesca F Trombetta Carlo Simone CS Venuto Ilaria I Saccheri Paola P Travan Luciana L Chiriacò Giovanni G

BMC sports science, medicine & rehabilitation 20170207

<h4>Background</h4>Low back pain (LBP) is common in athletes. LBP can be detrimental to athletic performance and health. Factors predisposing to LBP in athletes remain elusive and require further studies. We investigated whether carriage of a specific genotype and/or allele of vitamin D receptor gene (VDR) FokI polymorphism (rs2228570) was a risk factor for LBP in athletes of different sports disciplines.<h4>Methods</h4>This genotype/phenotype association case-control study included 60 Italian a ...[more]

PMID: 28184307

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Project description:The FokI vitamin D receptor (VDR) polymorphism results in different translation initiation sites on VDR. In the VDRff variant, initiation of translation occurs at the first ATG site, giving rise to a full length VDR protein of 427 amino acids. Conversely, in the VDRFF variant, translation begins at the second ATG site, resulting in a truncated protein with three less amino acids. Epidemiological studies have paradoxically implicated this polymorphism with increased breast cancer risk. 1?,25 (OH)(2)D(3), the active metabolite of vitamin D, is known to inhibit cell proliferation, induce apoptosis and potentiate differentiation in human breast cancer cells. It is well documented that 1?,25 (OH)(2)D(3) downregulates estrogen receptor ? expression and inhibits estrogen mediated signaling in these cells. The functional significance of the VDR FokI polymorphism in vitamin D action is undefined.To elucidate the functional role of FokI polymorphism in breast cancer, MCF-7-Vector, MCF-7-VDRff and MCF-7-VDRFF stable cell lines were established from parental MCF-7 cells as single-cell clones. In response to 1?,25 (OH)(2)D(3) treatments, cell growth was inhibited by 60% in VDRFF cells compared to 28% in VDRff cells. The induction of the vitamin D target gene CYP24A1 mRNA was 1.8 fold higher in VDRFF cells than in VDRff cells. Estrogen receptor-? protein expression was downregulated by 62% in VDRFF cells compared to 25% in VDRff cells. VDR protein stability was greater in MCF-7-VDRFF cells in the presence of cycloheximide. PCR array analyses of VDRff and VDRFF cells revealed increased basal expression levels of pro-inflammatory genes Cyclooxygenase-2, Interleukin-8 and Chemokine (C-C Motif) Ligand 2 in MCF-7-VDRff cells by 14, 52.7 and 5 fold, respectively.These results suggest that a VDRff genotype may play a role in amplifying aggressive breast cancer, paving the way for understanding why some breast cancer cells respond inefficiently to vitamin D treatment.

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Low back pain and FokI (rs2228570) polymorphism of vitamin D receptor in athletes.

Publications

Low back pain and FokI (rs2228570) polymorphism of vitamin D receptor in athletes.

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