Colombini Alessandra, Brayda-Bruno Marco, Lombardi Giovanni, Croiset Samantha Jennifer, Vrech Valentina, Maione Vincenzo, Banfi Giuseppe, Cauci Sabina
Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milano, Italy.
Department of Orthopedics and Traumatology - Vertebral surgery III - Scoliosis, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milano, Italy.
PLoS One. 2014 May 8;9(5):e97027. doi: 10.1371/journal.pone.0097027. eCollection 2014.
Alterations in vitamin D homeostasis, mainly involving its nuclear receptor (VDR), could have a role in the pathophysiology of the spine. The association between VDR polymorphisms and spine disorders has been analyzed in different ethnic groups, focusing on the functional FokI polymorphism. However, so far, inconsistent findings were reported. The aims of this study were to evaluate, in the Italian white population, the VDR FokI polymorphism frequencies distribution in subjects with clearly defined lumbar spinal pathologies compared to asymptomatic controls and to analyze the interplay of genetic and conventional risk factors. Using a case-control design, 267 patients with spinal disorders and 220 asymptomatic controls were enrolled, evaluating their exposition to putative risk factors. Patients' clinical assessment was performed by Magnetic Resonance Imaging. FokI polymorphism (rs2228570) was detected by PCR-RFLP. Genotypes were designated by a lowercase letter (f allele, T nucleotide) for the presence of the restriction site and by a capital letter (F allele, C nucleotide) for its absence. Family history, higher age and BMI, exposure to vibration, physical job demand, smoking habit and lower practice of leisure physical activity were associated with spinal disorders. The FF genotype and F allele represented approximately 2-fold risk factors to develop discopathies and/or osteochondrosis concomitant with disc herniation, while f allele was protective. In conclusion, the link we observed between VDR FokI variants and specific lumbar spine pathologies suggests that spinal tissue degeneration is influenced by the genetic background. Future studies should evaluate the signaling pathways involving alterations in VDR and influencing the development and/or progression of spine disorders.
维生素D内稳态的改变,主要涉及其核受体(VDR),可能在脊柱的病理生理学中起作用。VDR基因多态性与脊柱疾病之间的关联已在不同种族群体中进行了分析,重点是功能性FokI多态性。然而,到目前为止,报道的结果并不一致。本研究的目的是在意大利白人人群中,评估与无症状对照组相比,患有明确腰椎疾病的受试者中VDR FokI多态性频率分布,并分析遗传和传统风险因素之间的相互作用。采用病例对照设计,纳入了267例脊柱疾病患者和220例无症状对照,评估他们对假定风险因素的暴露情况。通过磁共振成像对患者进行临床评估。通过PCR-RFLP检测FokI多态性(rs2228570)。根据是否存在限制性位点,基因型用小写字母(f等位基因,T核苷酸)表示,不存在则用大写字母(F等位基因,C核苷酸)表示。家族史、较高的年龄和体重指数、接触振动、体力工作需求、吸烟习惯以及较低的休闲体育活动参与度与脊柱疾病有关。FF基因型和F等位基因是发生椎间盘疾病和/或伴有椎间盘突出的骨软骨病的约2倍风险因素,而f等位基因具有保护作用。总之,我们观察到的VDR FokI变体与特定腰椎疾病之间的联系表明,脊柱组织退变受遗传背景的影响。未来的研究应评估涉及VDR改变并影响脊柱疾病发生和/或进展的信号通路。