Research Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.
J Res Health Sci. 2024 Mar 18;24(1):e00603. doi: 10.34172/jrhs.2024.138.
Genetic polymorphisms are known to play a crucial role in the development of osteoporosis. Vitamin D regulates bone homeostasis through the vitamin D receptor (VDR). Reduced VDR activity increases osteoporosis risk. A case-control study.
This case-control study investigated the potential association between six single-nucleotide polymorphisms (SNPs) within the gene (rs11568820, rs4516035, rs2228570, rs1544410, rs7975232, and rs731236) and the occurrence of osteoporosis in Kerman province. The genotypes of the SNPs were analyzed using polymerase chain reaction-restriction fragment length polymorphism, tetra primer amplification refractory mutation system-PCR, and sequencing in two groups of osteoporosis patients (n=40) and controls (n=42). Additionally, the levels of calcium and vitamin D in the serum of the patients were measured, and the in silico analysis of the VDR structure and interaction was performed using I-TASSER, ProSA, PROCHECK, GeneMANIA, GTEx, and GPS 6.0.
None of the patients exhibited calcium or vitamin D deficiencies. Among the six SNPs, only the T allele in rs4516035, which leads to a shorter variant called VDRA, showed a significant association with susceptibility to osteoporosis (odds ratio=3.061, =0.007). The in silico analysis demonstrated that the 3D structure, expression, and post-transcriptional modification of VDRA are distinct from those of the more extended variant, VDRB1. VDRB1 is upregulated in sun-exposed skin, and its interactions with its partners differ from those of VDRA.
Despite adequate vitamin D levels, the VDRA variant, which has lower activity, could increase the predisposition to osteoporosis in the studied population. These findings clarify the importance of genetic screening for personalized medicine and the effectiveness of prevention and treatment strategies.
遗传多态性在骨质疏松症的发展中起着至关重要的作用。维生素 D 通过维生素 D 受体（VDR）调节骨稳态。VDR 活性降低会增加骨质疏松症的风险。一项病例对照研究。
本病例对照研究调查了基因内六个单核苷酸多态性（SNPs）（rs11568820、rs4516035、rs2228570、rs1544410、rs7975232 和 rs731236）与克尔曼省骨质疏松症发生之间的潜在关联。使用聚合酶链反应-限制性片段长度多态性、四引物扩增不可预知突变系统-聚合酶链反应和测序在两组骨质疏松症患者（n=40）和对照组（n=42）中分析 SNP 的基因型。此外，还测量了患者血清中的钙和维生素 D 水平，并使用 I-TASSER、ProSA、PROCHECK、GeneMANIA、GTEx 和 GPS 6.0 对 VDR 结构和相互作用进行了计算机模拟分析。
患者中没有钙或维生素 D 缺乏。在六个 SNP 中，只有 rs4516035 中的 T 等位基因与骨质疏松症易感性显著相关（优势比=3.061，=0.007），导致较短的变体称为 VDRA。计算机模拟分析表明，VDRA 的 3D 结构、表达和转录后修饰与更长变体 VDRB1 不同。VDRB1 在暴露于阳光下的皮肤中上调，其与伙伴的相互作用与 VDRA 不同。
尽管维生素 D 水平充足，但活性较低的 VDRA 变体可能会增加研究人群患骨质疏松症的易感性。这些发现阐明了遗传筛查在个性化医疗中的重要性，以及预防和治疗策略的有效性。
