背景:已知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D3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。研究设计:病例对照研究。
方法:这项病例对照研究调查了VDR基因中六个单核苷酸多态性(SNP)之间的潜在关联(rs11568820,rs4516035,rs2228570,rs1544410,rs7975232和rs731236)与克尔曼省骨质疏松症的发生。使用聚合酶链反应-限制性片段长度多态性分析SNP的基因型,四引物扩增难治性突变系统-PCR,并对两组骨质疏松症患者(n=40)和对照组(n=42)进行测序。此外,测量患者血清中钙和维生素D3的水平,并使用I-TASSER进行VDR结构和相互作用的计算机模拟分析,ProSA,PROCHECK,遗传狂躁症,GTEx,GPS6.0
结果:没有患者出现钙或维生素D3缺乏。在六个SNP中,只有rs4516035中的T等位基因,它导致一个称为VDRA的较短变体,与骨质疏松易感性显著相关(比值比=3.061,P=0.007)。计算机模拟分析表明,3D结构,表达式,VDRA的转录后修饰与更延伸的变体不同,VDRB1.VDRB1在暴露于阳光下的皮肤中上调,它与合作伙伴的互动不同于VDRA。
结论:尽管维生素D水平充足,VDRA变体,活性较低,可能会增加被研究人群骨质疏松症的易感性。这些发现阐明了基因筛查对个性化医疗的重要性以及预防和治疗策略的有效性。
BACKGROUND: Genetic polymorphisms are known to play a crucial role in the development of osteoporosis. Vitamin D3 regulates bone homeostasis through the vitamin D receptor (VDR). Reduced VDR activity increases osteoporosis risk. Study Design: A
case-control study.
METHODS: This
case-control study investigated the potential association between six single-nucleotide polymorphisms (SNPs) within the VDR 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 D3 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.
RESULTS: None of the patients exhibited calcium or vitamin D3 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, P=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.
CONCLUSIONS: 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.