Mashayekhi Sohail, Saberi Alia, Salehi Zivar, Biazar Gelareh, Mehrdel Roghayeh
Neurosciences Research Center, Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran.
Neurosciences Research Center, Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran; Department of Neurology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Clin Neurol Neurosurg. 2018 Feb;165:67-71. doi: 10.1016/j.clineuro.2017.12.024. Epub 2017 Dec 29.
Lumbar disc degeneration (LDD) occurs commonly in humans. Vitamin D metabolic and signaling pathway plays a significant role in intervertebral disc degeneration. The aim of this study was to evaluate the influence of the genetic polymorphism in the two key genes of 1,25-(OH)-D pathway, VDR (vitamin D receptor) and GC (group-specific component), in LDD development.
Two single-nucleotide polymorphisms, VDR rs2228570 (FokI) and GC rs7041, were genotyped in 180 patients with LDD and 230 healthy individuals. Genomic DNA was extracted from whole peripheral blood. VDR and GC genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
A significant difference in genotype distributions of rs2228570 in VDR and rs7041 in GC gene were observed between cases and controls (P = .01 and. 005, respectively). The VDR AA homozygous genotype was seen in 30(16.7%) patients with LDD and 20(8.7%) controls (codominant model: OR = 2.48; 95% CI 1.30-4.73, P = .005) with an estimated approximately 2.5-fold risk of developing LDD in individuals with this genotype. Moreover, higher grades of disc degeneration were more related to VDR A allele. The minor allele of GC rs7041 was associated with a decreased risk of LDD (OR = 0.69; 95% CI 0.44-0.82, P = .001).
In conclusion, our results suggest for the first time that the genetic variants of VDR and GC genes contribute to genetic predisposition to LDD in Iran. These findings need further validation in the large multicenter case-control studies.
腰椎间盘退变（LDD）在人类中普遍存在。维生素D代谢和信号通路在椎间盘退变中起重要作用。本研究旨在评估1,25 -（OH）-D通路的两个关键基因，即维生素D受体（VDR）和维生素D结合蛋白（GC）的基因多态性对LDD发生发展的影响。
对180例LDD患者和230例健康个体进行VDR rs2228570（FokI）和GC rs7041这两个单核苷酸多态性的基因分型。从外周全血中提取基因组DNA。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法进行VDR和GC基因分型。
病例组与对照组在VDR基因的rs2228570和GC基因的rs7041基因型分布上存在显著差异（分别为P = 0.01和0.005）。30例（16.7%）LDD患者和20例（8.7%）对照者出现VDR AA纯合基因型（共显性模型：OR = 2.48；95%CI 1.30 - 4.73，P = 0.005），该基因型个体发生LDD的风险估计约为2.5倍。此外，较高程度的椎间盘退变与VDR A等位基因更相关。GC rs7041的次要等位基因与LDD风险降低相关（OR = 0.69；95%CI 0.44 - 0.82，P = 0.001）。
总之，我们的结果首次表明VDR和GC基因的遗传变异在伊朗人群中对LDD的遗传易感性有影响。这些发现需要在大型多中心病例对照研究中进一步验证。
